126 results on '"Suxia Han"'
Search Results
2. Corrigendum to 'Promethazine inhibits proliferation and promotes apoptosis in colorectal cancer cells by suppressing the PI3K/AKT pathway' [Biomed. Pharmacotherapy 143(2021)112174]
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Xinyue Tan, Liuyun Gong, Xinyue Li, Xinyue Zhang, Jiahao Sun, Xuehui Luo, Qi Wang, Jie Chen, Lina Xie, and Suxia Han
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Therapeutics. Pharmacology ,RM1-950 - Published
- 2024
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3. An innovative gene expression modulating strategy by converting nucleic acids into HNC therapeutics using carrier-free nanoparticles
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Heyuan Liu, Yinong Huang, Zongfang Li, Suxia Han, Tianya Liu, and Qian Zhao
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derivatives of siRNA ,automatic assembly system ,siRNA clinical translation ,carrier-free nanoparticles ,anticancer therapeutics ,Immunologic diseases. Allergy ,RC581-607 - Abstract
BackgroundCell fate and microenvironmental changes resulting from aberrant expression of specific proteins in tumors are one of the major causes of inadequate anti-tumor immune response and poor prognosis in head and neck cancer (HNC). Eukaryotic initiation factor 3C (eIF3c) has emerged as a promising therapeutic target for HNC due to its ability to regulate protein expression levels in tumor cells, but its drug development is difficult to achieve by targeting traditional protein-protein interactions. siRNA has emerged as a highly promising modality for drug development targeting eIF3c, while its application is hindered by challenges pertaining to inadequate stability and insufficient concentration specifically within tumor sites.MethodWe employed a method to convert flexible siRNAs into stable and biologically active infinite Auric-sulfhydryl coordination supramolecular siRNAs (IacsRNAs). Through coordinated self-assembly, we successfully transformed eIF3C siRNAs into the carrier-free HNC nanotherapeutic agent Iacs-eif3c-RNA. The efficacy of this agent was evaluated in vivo using HNC xenograft models, demonstrating promising antitumor effects.ResultsIacs-eif3c-RNA demonstrated the ability to overcome the pharmacological obstacle associated with targeting eIF3C, resulting in a significant reduction in eIF3C expression within tumor tissues, as well as effective tumor cell proliferating suppression and apoptosis promotion. In comparison to monotherapy utilizing the chemotherapeutic agent cisplatin, Iacs-eif3c-RNA exhibited superior anti-tumor efficacy and favorable biosafety.ConclusionThe utilization of Iacs-eif3c-RNA as a carrier-free nanotherapeutic agent presents a promising and innovative approach for addressing HNC treating challenges. Moreover, this strategy demonstrates potential for the translation of therapeutic siRNAs into clinical drugs, extending its applicability to the treatment of other cancers and various diseases.
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- 2024
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4. Cocktail hepatocarcinoma therapy by a super-assembled nano-pill targeting XPO1 and ATR synergistically
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Liuyun Gong, Yinliang Lu, Jing Wang, Xinyue Li, Jing Zhao, Yuetong Chen, Rongze Ma, Jinlu Ma, Tianya Liu, and Suxia Han
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Liver cancer ,Drug combination ,Cancer therapy ,ATR inhibitor ,XPO1 inhibitor ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Intensive cancer treatment with drug combination is widely exploited in the clinic but suffers from inconsistent pharmacokinetics among different therapeutic agents. To overcome it, the emerging nanomedicine offers an unparalleled opportunity for encapsulating multiple drugs in a nano-carrier. Herein, a two-step super-assembled strategy was performed to unify the pharmacokinetics of a peptide and a small molecular compound. In this proof-of-concept study, the bioinformatics analysis firstly revealed the potential synergies towards hepatoma therapy for the associative inhibition of exportin 1 (XPO1) and ataxia telangiectasia mutated-Rad3-related (ATR), and then a super-assembled nano-pill (gold nano drug carrier loaded AZD6738 and 97−110 amino acids of apoptin (AP) (AA@G)) was constructed through camouflaging AZD6738 (ATR small-molecule inhibitor)-binding human serum albumin onto the AP-Au supramolecular nanoparticle. As expected, both in vitro and in vivo experiment results verified that the AA@G possessed extraordinary biocompatibility and enhanced therapeutic effect through inducing cell cycle arrest, promoting DNA damage and inhibiting DNA repair of hepatoma cell. This work not only provides a co-delivery strategy for intensive liver cancer treatment with the clinical translational potential, but develops a common approach to unify the pharmacokinetics of peptide and small-molecular compounds, thereby extending the scope of drugs for developing the advanced combination therapy.
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- 2023
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5. Repurposing econazole as a pharmacological autophagy inhibitor to treat pancreatic ductal adenocarcinoma
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Ningna Weng, Siyuan Qin, Jiayang Liu, Xing Huang, Jingwen Jiang, Li Zhou, Zhe Zhang, Na Xie, Kui Wang, Ping Jin, Maochao Luo, Liyuan Peng, Edouard C. Nice, Ajay Goel, Suxia Han, Canhua Huang, and Qing Zhu
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Econazole ,Autophagy ,PDAC ,ATF3 ,AKT ,Organoid ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Pancreatic ductal adenocarcinoma (PDAC) is characterized by the highest mortality among carcinomas. The pathogenesis of PDAC requires elevated autophagy, inhibition of which using hydroxychloroquine has shown promise. However, current realization is impeded by its suboptimal use and unpredictable toxicity. Attempts to identify novel autophagy-modulating agents from already approved drugs offer a rapid and accessible approach. Here, using a patient-derived organoid model, we performed a comparative analysis of therapeutic responses among various antimalarial/fungal/parasitic/viral agents, through which econazole (ECON), an antifungal compound, emerged as the top candidate. Further testing in cell-line and xenograft models of PDAC validated this activity, which occurred as a direct consequence of dysfunctional autophagy. More specifically, ECON boosted autophagy initiation but blocked lysosome biogenesis. RNA sequencing analysis revealed that this autophagic induction was largely attributed to the altered expression of activation transcription factor 3 (ATF3). Increased nuclear import of ATF3 and its transcriptional repression of inhibitor of differentiation-1 (ID-1) led to inactivation of the AKT/mammalian target of rapamycin (mTOR) pathway, thus giving rise to autophagosome accumulation in PDAC cells. The magnitude of the increase in autophagosomes was sufficient to elicit ER stress-mediated apoptosis. Furthermore, ECON, as an autophagy inhibitor, exhibited synergistic effects with trametinib on PDAC. This study provides direct preclinical and experimental evidence for the therapeutic efficacy of ECON in PDAC treatment and reveals a mechanism whereby ECON inhibits PDAC growth.
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- 2022
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6. Docetaxel-induced cognitive impairment in rats can be ameliorated by edaravone dexborneol: Evidence from the indicators of biological behavior and anisotropic fraction
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Ping Liu, Hai Liu, Lijun Wei, Xun Shi, Wei Wang, Shengxiang Yan, Wenya Zhou, Jiangong Zhang, and Suxia Han
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edaravone dexborneol ,cognitive impairment ,diffusion tensor imaging ,hippocampus ,fractional anisotropy ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
ObjectiveThis study aimed to investigate the effect of Edaravone Dexborneol (ED) on impaired learning and memory in docetaxel (DTX)-treated rats using cognitive behavior assessments and magnetic resonance diffusion tensor imaging (DTI).Materials and methodsIn total, 24 male Sprague–Dawley rats were divided into control, low-dose DTX (L-DTX) model, and high-dose DTX(H-DTX) model groups, with eight rats in each group, numbered 1–8. The rats were intraperitoneally injected with 1.5 mL of either normal saline (control group), or 3 mg/kg and 6 mg/kg DTX (L-DTX and H-DTX groups, respectively), once a week for 4 weeks. The learning and memory abilities of each group were tested using a water maze. At the end of the water maze test, rats 1–4 in each group were treated with ED (3 mg/kg, 1 mL), and rats 5–8 were injected with an equal volume of normal saline once a day for 2 weeks. The learning and memory abilities of each group were evaluated again using the water maze test, and the image differences in the hippocampus of each group were analyzed using DTI.Results(1) H-DTX group (32.33 ± 7.83) had the longest escape latency, followed by the L-DTX group (27.49 ± 7.32), and the Control group (24.52 ± 8.11) having the shortest, with the difference being statistically significant (p
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- 2023
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7. Engineering of gold nanorods as multifunctional theranostic agent for photothermal-enhanced radiotherapy of cancer
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Lina Xie, Xia Ying, Xinyue Li, Xinyue Tan, Tianzi Zhang, Xujia Zhang, Wen Cai, Feifei An, Xiaoli Liu, and Suxia Han
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Gold nanorods (GNRs) ,Photothermal therapy (PTT) ,Radiotherapy (RT) ,Multi-modal imaging ,Aggregation-induced emission (AIE) ,Materials of engineering and construction. Mechanics of materials ,TA401-492 - Abstract
Radiotherapy (RT) is an important method in cancer treatment. Devising conveniently synthesizable and smart multifunctional radiosensitizers is of tremendous significance to improve the cure rate of RT. Gold nanorods (GNRs), which exhibit high X-ray absorption capacity and near-infrared (NIR) photothermal conversion effectiveness, could be utilized as radiosensitizers. In the present study, an all-in-one theranostic nanoagent for photothermal-enhanced RT of cancer was devised based on engineered GNRs with aggregation-induced emission (AIE) attributes. This nanoagent-mediated photothermal therapy (PTT) in combination with RT (PTT-RT) demonstrated excellent photothermal-enhanced RT effect by significantly inhibiting migration and invasion, increasing reactive oxygen species (ROS) production and causing more DNA damage in two different pathological types of cell lines of cervical cancer, compared with mere RT. The PTT-RT based on this nanoagent further showed enhanced RT effect in vivo, and increased the production of some metabolites remarkablely enriched in the phenylalanine metabolism pathway revealed by the metabolomics analysis, compared with RT alone. Meanwhile, this nanoagent exhibited excellent computed tomography imaging (CTI)/photoacoustic imaging (PAI)/fluorescence imaging (FLI)/photothermal imaging (PTI) multi-modal imaging capability. The present research provides a multifunctional platform for optimizing the efficacy of RT and enriches the mechanism study for GNRs-mediated photothermal-enhanced RT.
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- 2023
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8. Preparation, toxicity reduction and radiation therapy application of gold nanorods
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Lina Xie, Xujia Zhang, Chengchao Chu, Yingqi Dong, Tianzi Zhang, Xinyue Li, Gang Liu, Wen Cai, and Suxia Han
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Gold nanorods (GNRs) ,Preparation ,Toxicity reduction ,Radiation sensitization ,Radiation therapy ,Biotechnology ,TP248.13-248.65 ,Medical technology ,R855-855.5 - Abstract
Abstract Gold nanorods (GNRs) have a broad application prospect in biomedical fields because of their unique properties and controllable surface modification. The element aurum (Au) with high atomic number (high-Z) render GNRs ideal radiosensitive materials for radiation therapy and computed tomography (CT) imaging. Besides, GNRs have the capability of efficiently converting light energy to heat in the near-infrared (NIR) region for photothermal therapy. Although there are more and more researches on GNRs for radiation therapy, how to improve their biocompatibility and how to efficiently utilize them for radiation therapy should be further studied. This review will focuse on the research progress regarding the preparation and toxicity reduction of GNRs, as well as GNRs-mediated radiation therapy. Graphical Abstract
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- 2021
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9. SPOP promotes CDCA5 degradation to regulate prostate cancer progression via the AKT pathway
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Zhenzhen Luo, Jing Wang, Yue Zhu, Xiao Sun, Chenchen He, Mengjiao Cai, Jinlu Ma, Yi Wang, and Suxia Han
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Prostate cancer ,SPOP ,CDCA5 ,Ubiquitin degradation ,Essential gene ,AKT ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
The E3 ubiquitin ligase adaptor Speckle-type POZ protein (SPOP) plays an important tumour suppressor role in prostate cancers (PCa), with mutation rate up to 15%. However, how SPOP mutations regulate prostate tumorigenesis remains elusive. Here, we report the identification of cell division cycle associated 5 (CDCA5) as a SPOP substrate. We found that SPOP interacts with CDCA5 and promotes its polyubiquitin degradation in a degron-dependent manner. This effect was greatly impaired by introducing PCa associated SPOP mutations. Importantly, we found that CDCA5 was essential for PCa cells to survive and proliferate. CDCA5 depletion in PCa cells led to cessation of proliferation, G2M arrest, severe sister chromatid aggregation disturbance, and apoptosis. we also found that CDCA5 knockdown decreased the protein expression of p-GSK3β, increased the activity of caspase-3, caspase-9, and the Bax/Bcl-2 ratio. Besides, we confirmed that CDCA5 interrupted cancer cell behavior via the AKT pathway. In contrast, silencing SPOP or overexpressing CDCA5 increased cell proliferation. Consistently, depleting SPOP along with CDCA5, or overexpressing CDCA5 along with SPOP also caused the growth of cells repressed. Consistent with the functional role of CDCA5, the mRNA and protein levels of CDCA5 were significantly increased in PCa, compared to normal tissues, and its high expression was associated with more severe lymph node metastasis, higher Gleason score, and poorer prognosis. Together, our data showed that SPOP plays a crucial role in inhibiting tumorigenesis and partly achieved this by promoting the degradation of oncoprotein CDCA5.
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- 2021
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10. Targeting EIF3C to suppress the development and progression of nasopharyngeal carcinoma
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Qian Zhao, Xuehui Luo, Honghui Li, Yanxia Bai, Qian Chen, Ming Yang, Bei Pei, Chongwen Xu, and Suxia Han
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EIF3C ,cancer therapy ,head and neck cancer ,pharyngeal cancer ,nucleic acid drug ,Biotechnology ,TP248.13-248.65 - Abstract
Nasopharyngeal carcinoma occurs in many parts of the pars nasalis pharyngis, and the pathological type is mainly squamous cell carcinoma. Because of the special position of nasopharynx, breathing, pronunciation and daily life will be seriously affected. At present, the research direction of nasopharyngeal carcinoma is mainly to explore the law of tumor cell proliferation and migration, study the molecular mechanism, master its biological behavior and clinical significance, try to find therapeutic targets, and further improve the level of tumor treatment. However, the pathologic structure and molecular mechanism of nasopharyngeal carcinoma have not been fully elucidated. In this study, the Lentivirus-mediated EIF3C shRNA vector (L.V-shEIF3C) was constructed to down-regulate the expression of EIF3C in human pharyngeal squamous carcinoma cell FaDu and the human nasopharyngeal carcinoma cell 5-8F, it was found that down-regulation of EIF3C could significantly inhibit the cell proliferation, promote cell apoptosis, induce cell cycle arrest, and inhibit the formation and growth of tumors in mouse models. This study provides strong evidence that EIF3C is a key gene driving the development and progression of head and neck cancer, which is of great significance for the diagnosis, prognosis or treatment of tumors, suggesting that EIF3C may become a valuable therapeutic development and intervention target.
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- 2022
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11. Immune-Associated Gene Signatures Serve as a Promising Biomarker of Immunotherapeutic Prognosis for Renal Clear Cell Carcinoma
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Qi Wang, Hanmin Tang, Xuehui Luo, Jie Chen, Xinyue Zhang, Xinyue Li, Yuesen Li, Yuetong Chen, Yungang Xu, and Suxia Han
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renal clear cell carcinoma (ccRCC) ,immune checkpoint inhibition ,IRPDGs ,tumor microenvironment ,prognostic biomarker ,Immunologic diseases. Allergy ,RC581-607 - Abstract
As the most common type of renal cell carcinoma (RCC), the renal clear cell carcinoma (ccRCC) is highly malignant and insensitive to chemotherapy or radiotherapy. Although systemic immunotherapies have been successfully applied to ccRCC in recent years, screening for patients who can benefit most from these therapies is still essential and challenging due to immunological heterogeneity of ccRCC patients. To this end, we implemented a series of deep investigation on the expression and clinic data of ccRCC from The Cancer Genome Atlas (TCGA) International Consortium for Cancer Genomics (ICGC). We identified a total of 946 immune-related genes that were differentially expressed. Among them, five independent genes, including SHC1, WNT5A, NRP1, TGFA, and IL4R, were significantly associated with survival and used to construct the immune-related prognostic differential gene signature (IRPDGs). Then the ccRCC patients were categorized into high-risk and low-risk subgroups based on the median risk score of the IRPDGs. IRPDGs subgroups displays distinct genomic and immunological characteristics. Known immunotherapy-related genes show different mutation burden, wherein the mutation rate of VHL was higher than 40% in the two IRPDGs subgroups, and SETD2 and BAP1 mutations differed most between two groups with higher frequency in the high-risk subgroup. Moreover, IRPDGs subgroups had different abundance in tumor-infiltrating immune cells (TIICs) with distinct immunotherapy efficacy. Plasma cells, regulatory cells (Tregs), follicular helper T cells (Tfh), and M0 macrophages were enriched in the high-risk group with a higher tumor immune dysfunction and rejection (TIDE) score. In contrast, the low-risk group had abundant M1 macrophages, mast cell resting and dendritic cell resting infiltrates with lower TIDE score and benefited more from immune checkpoint inhibitors (ICI) treatment. Compared with other biomarkers, such as TIDE and tumor inflammatory signatures (TIS), IRPDGs demonstrated to be a better biomarker for assessing the prognosis of ccRCC and the efficacy of ICI treatment with the promise in screening precise patients for specific immunotherapies.
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- 2022
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12. A Novel Necroptosis-Related lncRNA Signature Predicts the Prognosis of Lung Adenocarcinoma
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Yinliang Lu, XueHui Luo, Qi Wang, Jie Chen, Xinyue Zhang, YueSen Li, Yuetong Chen, Xinyue Li, and Suxia Han
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lung adenocarcinoma ,necroptosis gene ,long noncoding RNA ,tumor immune microenvironment ,prognostic signature ,Genetics ,QH426-470 - Abstract
Background: Necroptosis is closely related to the tumorigenesis and development of cancer. An increasing number of studies have demonstrated that targeting necroptosis could be a novel treatment strategy for cancer. However, the predictive potential of necroptosis-related long noncoding RNAs (lncRNAs) in lung adenocarcinoma (LUAD) still needs to be clarified. This study aimed to construct a prognostic signature based on necroptosis-related lncRNAs to predict the prognosis of LUAD.Methods: We downloaded RNA sequencing data from The Cancer Genome Atlas database. Co-expression network analysis, univariate Cox regression, and least absolute shrinkage and selection operator were adopted to identify necroptosis-related prognostic lncRNAs. We constructed the predictive signature by multivariate Cox regression. Kaplan–Meier analysis, time-dependent receiver operating characteristics, nomogram, and calibration curves were used to validate and evaluate the signature. Subsequently, we used gene set enrichment analysis (GSEA) and single-sample gene set enrichment analysis (ssGSEA) to explore the relationship between the predictive signature and tumor immune microenvironment of risk groups. Finally, the correlation between the predictive signature and immune checkpoint expression of LUAD patients was also analyzed.Results: We constructed a signature composed of 7 necroptosis-related lncRNAs (AC026355.2, AC099850.3, AF131215.5, UST-AS2, ARHGAP26-AS1, FAM83A-AS1, and AC010999.2). The signature could serve as an independent predictor for LUAD patients. Compared with clinicopathological variables, the necroptosis-related lncRNA signature has a higher diagnostic efficiency, with the area under the receiver operating characteristic curve being 0.723. Meanwhile, when patients were stratified according to different clinicopathological variables, the overall survival of patients in the high-risk group was shorter than that of those in the low-risk group. GSEA showed that tumor- and immune-related pathways were mainly enriched in the low-risk group. ssGSEA further confirmed that the predictive signature was significantly related to the immune status of LUAD patients. The immune checkpoint analysis displayed that low-risk patients had a higher immune checkpoint expression, such as CTLA-4, HAVCR2, PD-1, and TIGIT. This suggested that immunological function is more active in the low-risk group LUAD patients who might benefit from checkpoint blockade immunotherapies.Conclusion: The predictive signature can independently predict the prognosis of LUAD, helps elucidate the mechanism of necroptosis-related lncRNAs in LUAD, and provides immunotherapy guidance for patients with LUAD.
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- 2022
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13. Tamoxifen induces fatty liver disease in breast cancer through the MAPK8/FoxO pathway
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Liuyun Gong, Hanmin Tang, Zhenzhen Luo, Xiao Sun, Xinyue Tan, Lina Xie, Yutiantian Lei, Mengjiao Cai, Chenchen He, Jinlu Ma, and Suxia Han
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bioinformatics analysis ,breast cancer ,fatty liver ,FoxO signaling pathway ,MAPK8 ,TAM ,Medicine (General) ,R5-920 - Abstract
Abstract Background Prevention of metabolic complications of long‐term adjuvant endocrine therapy in breast cancers remained a challenge. We aimed to investigate the molecular mechanism in the development of tamoxifen (TAM)‐induced fatty liver in both estrogen receptor (ER)‐positive and ER‐negative breast cancer. Methods and results First, the direct protein targets (DPTs) of TAM were identified using DrugBank5.1.7. We found that mitogen‐activated protein kinase 8 (MAPK8) was one DPT of TAM. We identified significant genes in breast cancer and fatty liver disease (FLD) using the MalaCards human disease database. Next, we analyzed the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of those significant genes in breast cancer and FLD using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING). We found that overlapping KEGG pathways in these two diseases were MAPK signaling pathway, Forkhead box O (FoxO) signaling pathway, HIF‐1 signaling pathway, AGE‐RAGE signaling pathway in diabetic complications, and PI3K‐Akt signaling pathway. Furthermore, the KEGG Mapper showed that the MAPK signaling pathway was related to the FoxO signaling pathway. Finally, the functional relevance of breast cancer and TAM‐induced FLD was validated by Western blot analysis. We verified that TAM may induce fatty liver in breast cancer through the MAPK8/FoxO signaling pathway. Conclusion Bioinformatics analysis combined with conventional experiments may improve our understanding of the molecular mechanisms underlying side effects of cancer drugs, thereby making this method a new paradigm for guiding future studies on this issue.
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- 2020
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14. An Apoptosis-Related Gene Prognostic Index for Colon Cancer
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Hanmin Tang, Jing Wang, Xuehui Luo, Qi Wang, Jie Chen, Xinyue Zhang, Qiuting Li, Chengyi Gao, Yuesen Li, and Suxia Han
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apoptosis gene ,prognostic index ,colon cancer ,tumor microenvironment ,treatment ,nomograms ,Biology (General) ,QH301-705.5 - Abstract
Purpose: To construct an apoptosis-related gene prognostic index (ARGPI) for colon cancer, and clarify the molecular and immune characteristics of the risk subgroup as defined by the prognostic index and the benefits of adjuvant chemotherapy. Integrating the prognostic index and clinicopathological risk factors to better evaluate the prognosis of patients with colon cancer.Methods: Based on the colon adenocarcinoma data in the TCGA database, 20 apoptosis-related hub genes were screened by weighted gene co-expression network analysis (WGCNA). Five genes constituting the prognosis model were determined by Cox regression and verified by the Gene Expression Omnibus (GEO) dataset. Then the molecular and immune characteristics of risk subgroups defined by the prognostic index and the benefits of adjuvant chemotherapy were analyzed. Finally, nomograms integrating ARGPI and four clinicopathological risk factors were used to evaluate the prognosis of patients with colon cancer.Results: The ARGPI was constructed based on the FAS, VWA5A, SPTBN2, PCK1, and TIMP1 genes. In the TCGA cohort, patients in the low-risk subgroup had a longer progression-free interval (PFI) than patients in the high-risk subgroup, which coincided with the results of the GEO cohort. The comprehensive results showed that the high-risk score was related to the enrichment of the cell cycle pathway, high mutation rate of TP53 and KRAS, high infiltration of T regulatory cells (Tregs), immunosuppressive state, and less chemotherapeutic benefit. However, low-risk scores are related to drug metabolism-related pathways, low TP53 and KRAS mutation rates, high infiltration of plasma cells, more resting CD4 memory cells and eosinophils, active immune function, and better chemotherapeutic benefits. Receiver operating characteristic curve of two-year progress prediction evaluation showed that the ARGPI had higher prognostic accuracy than TNM staging. Nomograms integrating ARGPI and clinicopathological risk factors can better evaluate the prognosis of patients with colon cancer.Conclusions: The ARGPI is a promising biomarker for determining risk of colon cancer progression, molecular and immune characteristics, and chemotherapeutic benefit. This is a reliable method to predict the prognosis of colon cancer patients. It also can assist doctors in formulating more effective treatment strategies.
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- 2021
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15. Promethazine inhibits proliferation and promotes apoptosis in colorectal cancer cells by suppressing the PI3K/AKT pathway
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Xinyue Tan, Liuyun Gong, Xinyue Li, Xinyue Zhang, Jiahao Sun, Xuehui Luo, Qi Wang, Jie Chen, Lina Xie, and Suxia Han
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colorectal cancer ,promethazine ,apoptosis ,PI3K/AKT pathway ,drug repurposing ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Aim: To elucidate the potential effect of promethazine on colorectal cancer (CRC) cells and the underlying mechanism. Materials and methods: Targets of the drug promethazine (PMTZ) were identified by DrugBank and comparative toxicogenomic databases (CTD), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was performed with STRING software. The effects of PMTZ were predicted to be associated with the PI3K/AKT pathway. Cell Counting Kit 8 (CCK-8) assays were used to evaluate the effects of different concentrations of PMTZ on the proliferation of various types of CRC cells. Flow cytometry and Western blotting analyses were used to detect the degree of CRC cell apoptosis and the expression of the apoptosis-related proteins Bcl-2, Bax and caspase-3 after PMTZ treatment. The expression levels of PI3K/AKT pathway-related proteins [PI3K, AKT, phosphorylated (P)-PI3K and p-AKT] in CRC cells treated with PMTZ were analyzed by Western blotting. Results: PMTZ inhibited the proliferation and promoted the apoptosis of CRC cells and suppressed the activation of the PI3K/AKT signaling pathway in a dose-dependent manner. Discussion and conclusions: PMTZ may suppress the proliferation and induce the apoptosis of CRC cells by inhibiting the PI3K/ AKT signaling pathway. This study reported, for the first time, the function of PMTZ in CRC cells and the underlying mechanism and further confirmed the potential antitumor effects of phenothiazine. The combination of bioinformatics analyses and experiments provides informative evidence for the reuse of drugs and the development of new drugs.
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- 2021
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16. A Novel Immune Gene-Related Prognostic Score Predicts Survival and Immunotherapy Response in Glioma
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Xuehui Luo, Qi Wang, Hanmin Tang, Yuetong Chen, Xinyue Li, Jie Chen, Xinyue Zhang, Yuesen Li, Jiahao Sun, and Suxia Han
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RNA sequencing ,immune-related gene ,prognostic biomarker ,glioma ,immune checkpoint blockade ,tumor immune microenvironment ,Medicine (General) ,R5-920 - Abstract
Background and Objectives: The clinical prognosis and survival prediction of glioma based on gene signatures derived from heterogeneous tumor cells are unsatisfactory. This study aimed to construct an immune gene-related prognostic score model to predict the prognosis of glioma and identify patients who may benefit from immunotherapy. Methods: 23 immune-related genes (IRGs) associated with glioma prognosis were identified through weighted gene co-expression network analysis (WGCNA) and Univariate Cox regression analysis based on large-scale RNA-seq data. Eight IRGs were retained as candidate predictors and formed an immune gene-related prognostic score (IGRPS) by multifactorial Cox regression analysis. The potential efficacy of immune checkpoint blockade (ICB) therapy of different subgroups was compared by The Tumor Immune Dysfunction and Exclusion (TIDE) algorithm. We further adopted a series of bioinformatic methods to characterize the differences in clinicopathological features and the immune microenvironment between the different risk groups. Finally, a nomogram integrating IGRPS and clinicopathological characteristics was built to accurately predict the prognosis of glioma. Results: Patients in the low-risk group had a better prognosis than those in the high-risk group. Patients in the high-risk group showed higher TIDE scores and poorer responses to ICB therapy, while patients in the low-risk group may benefit more from ICB therapy. The distribution of age and tumor grade between the two subgroups was significantly different. Patients with low IGRPS harbor a high proportion of natural killer cells and are sensitive to ICB treatment. While patients with high IGRPS display relatively poor prognosis, a higher expression level of DNA mismatch repair genes, high infiltrating of immunosuppressive cells, and poor ICB therapeutic outcomes. Conclusions: We demonstrated that the IGRPS model can independently predict the clinical prognosis as well as the ICB therapy responses of glioma patients, thus having important implications on the design of immune-based therapeutic strategies.
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- 2022
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17. The SPOP-ITCH Signaling Axis Protects Against Prostate Cancer Metastasis
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Jinlu Ma, Mengjiao Cai, Yaqi Mo, Joshua S. Fried, Xinyue Tan, Yuan Ma, Jie Chen, Suxia Han, and Bo Xu
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SPOP ,ubiquitylation ,prostate cancer ,ITCH ,metastasis ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Prostate cancer is one of the most common causes of cancer incidence and death in men, with the mortality caused primarily by the late-stage and metastatic forms of the disease. The mechanisms and molecular markers for prostate cancer metastasis are not fully understood. Speckle type Poz Protein (SPOP) is an E3 ubiquitin ligase adaptor that is often mutated in prostate cancer. In this study, we sequenced the SPOP gene in 198 prostate cancer patients and found 16 mutations in the cohort. Multivariate analysis revealed that SPOP mutations correlated with the clinical stage of the disease and strongly with metastasis. We identified ITCH as a candidate protein for SPOP-mediated degradation via mass spectrometry. We demonstrated the interaction between SPOP and ITCH, and found that the SPOP F133L mutation disrupted the SPOP-ITCH interaction, leading to a subsequent increase in the ITCH protein level. Further, we found that the SPOP knockdown led to higher levels of Epithelial- mesenchymal transition (EMT) proteins and increased cell invasion. Together, our results highlight the functional significance of the SPOP-ITCH pathway in prostate cancer metastasis.
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- 2021
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18. Propranolol selectively inhibits cervical cancer cell growth by suppressing the cGMP/PKG pathway
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Liuyun Gong, Yutiantian Lei, Xinyue Tan, Yiping Dong, Zhenzhen Luo, Dan Zhang, and Suxia Han
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Propranolol ,Cervical cancer ,Bioinformatical analysis ,Proliferation ,Apoptosis ,cGMP-PKG signaling pathway ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Aim: To observe the effect of propranolol in cervical cancer and investigate the mechanism of the effect. Methods and Results: We found 5 direct protein targets (DPTs) of propranolol (PRO) by DrugBank5.0 firstly. Next, we analyzed protein-protein interaction (PPI) network and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of PRO DPTs and the result showed that PRO was linked with cGMP/PKG pathway. Then, we recognized the top 38 upexpressed genes of cervical cancer (CC) based original microarray datasets (GSE7803, GSE9750, GSE39001 and GSE63514). Further, we analyzed the biological process with the 38 overexpressed genes by STRING. We found some of overexpressed genes of CC participated in GMP biosynthetic process. Lastly, the function of PRO in CC was validated by MTT assay, Western blotting, flow cytometry and colony formation assay methods. We verified PRO can suppress cGMP/PKG pathway then inhibits CC cell growth. Conclusion: The bioinformatical analysis combine with traditional experiment can help us understanding potential molecular mechanism about how PRO acting in CC. This method is a new paradigm which can guide future researches about mechanism in existing diseases and drugs.
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- 2019
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19. Transcriptome‐wide association study identifies multiple genes and pathways associated with pancreatic cancer
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Liuyun Gong, Dan Zhang, Yutiantian Lei, Yuanjie Qian, Xinyue Tan, and Suxia Han
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pancreatic cancer ,genome‐wide association study ,transcriptome‐wide association study ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Aim To identify novel candidate genes for pancreatic cancer. Methods We performed a transcriptome‐wide association study (TWAS) analysis of pancreatic cancer (PC). GWAS summary data were driven from the published studies of PC, totally involving 558 542 SNPs in 1896 individuals with pancreatic cancer and 1939 healthy controls. FUSION software was applied to the PC GWAS summary data for tissue‐related TWAS analysis, including whole blood, peripheral blood, adipose, and pancreas. The functional relevance of identified genes with PC was further validated by Oncomine, STRING, and CluePedia tool. Results Transcriptome‐wide association study analysis identified 19 genes significantly associated with PC, such as LRP5L (P value = 5.21 × 10‐5), SOX4 (P value = 3.2 × 10‐4), and EGLN3 (P value = 6.2 × 10‐3). KEGG pathway enrichment analysis detected several PC‐associated pathways, such as One carbon pool by folate (P value = 1.60 × 10‐16), Cell cycle (P value = 1.27 × 10‐7), TGF‐beta signaling pathway (P value = 4.64 × 10‐6). Further comparing the 19 genes with previously identified overexpressed genes in PC patients found one overlapped gene SOX4. Conclusion We identified some novel candidate genes and pathways associated with PC. Our results provide novel clues for the genetic mechanism studies of pancreatic cancer.
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- 2018
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20. Linc00963 Promote Cell Proliferation and Tumor Growth in Castration-Resistant Prostate Cancer by Modulating miR-655/TRIM24 Axis
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Minghua Bai, Chenchen He, Shengjia Shi, Mincong Wang, Jinlu Ma, Pengtao Yang, Yiping Dong, Xingyi Mou, and Suxia Han
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Linc00963 ,TRIM24 ,miR-655 ,proliferation ,CRPC ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Previous studies have shown that both long intergenic non-coding RNA 00963 (Linc00963) and tripartite motif containing 24 (TRIM24) are activators of the PI3K/AKT pathway, and both are involved in the carcinogenesis and progression of prostate cancer. However, the regulatory mechanisms between Linc00963 and TRIM24 are still unclear. In this study, we aimed to elucidate the underlying relationship between Linc00963 and TRIM24 in castration-resistant prostate cancer (CRPC). We found that TRIM24, an established oncogene in CRPC, was positively correlated with Linc00963 in prostate cancer tissues. In addition, TRIM24 was positively regulated by Lin00963 in CRPC cells. Mechanistically, TRIM24 was the direct target of microRNA-655 (miR-655) in CRPC cells, and Linc00963 could competitively bind miR-655 and upregulate TRIM24 expression. Using gain- and loss-of- function assays and rescue assays, we identified that miR-655 inhibits TRIM24 expression and cell proliferation and colony forming ability in CRPC, and that Linc00963 promotes TRIM24 expression, cell proliferation, and colony forming ability of CRPC cells by directly suppressing miR-655 expression. We further identified that Linc00963 could promote tumor growth of CRPC cells by inhibiting miR-655 and upregulating TRIM24 axis in vivo. Taken together, our study reveals a new mechanism for the Linc00963/miR-655/TRIM24 competing endogenous RNA (ceRNA) network in accelerating cell proliferation in CRPC in vitro and in vivo, and suggests that Linc00963 could be considered a novel therapeutic target for CRPC.
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- 2021
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21. Integrating Genome-Wide Association Studies and Gene Expression Profiles With Chemical-Genes Interaction Networks to Identify Chemicals Associated With Colorectal Cancer
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Xinyue Tan, Hanmin Tang, Liuyun Gong, Lina Xie, Yutiantian Lei, Zhenzhen Luo, Chenchen He, Jinlu Ma, and Suxia Han
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colorectal cancer ,genome-wide association study ,transcriptome-wide association study ,gene set enrichment analysis ,comparative toxicogenomics database ,Genetics ,QH426-470 - Abstract
Colorectal cancer (CRC) is the third most common cancer and has the second highest mortality rate in global cancer. Exploring the associations between chemicals and CRC has great significance in prophylaxis and therapy of tumor diseases. This study aims to explore the relationships between CRC and environmental chemicals on genetic basis by bioinformatics analysis. The genome-wide association study (GWAS) datasets for CRC were obtained from the UK Biobank. The GWAS data for colon cancer (category C18) includes 2,581 individuals and 449,683 controls, while that of rectal cancer (category C20) includes 1,244 individuals and 451,020 controls. In addition, we derived CRC gene expression datasets from the NCBI-GEO (GSE106582). The chemicals related gene sets were acquired from the comparative toxicogenomics database (CTD). Transcriptome-wide association study (TWAS) analysis was applied to CRC GWAS summary data and calculated the expression association testing statistics by FUSION software. We performed chemicals related gene set enrichment analysis (GSEA) by integrating GWAS summary data, mRNA expression profiles of CRC and the CTD chemical-gene interaction networks to identify relationships between chemicals and genes of CRC. We observed several significant correlations between chemicals and CRC. Meanwhile, we also detected 5 common chemicals between colon and rectal cancer, including methylnitronitrosoguanidine, isoniazid, PD 0325901, sulindac sulfide, and importazole. Our study performed TWAS and GSEA analysis, linked prior knowledge to newly generated data and thereby helped identifying chemicals related to tumor genes, which provides new clues for revealing the associations between environmental chemicals and cancer.
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- 2020
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22. Long Non-coding RNA SNHG17 Promotes Cell Proliferation and Invasion in Castration-Resistant Prostate Cancer by Targeting the miR-144/CD51 Axis
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Minghua Bai, Yutiantian Lei, Mincong Wang, Jinlu Ma, Pengtao Yang, Xingyi Mou, Yiping Dong, and Suxia Han
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SNHG17 ,CD51 ,miR-144 ,CRPC ,proliferation ,Genetics ,QH426-470 - Abstract
Previously, we found that the expression of long non-coding RNA (lncRNA) small nucleolar RNA host gene 17 (SNHG17) was up-regulated in castration-resistant prostate cancer (CRPC) cells compared to that in hormone sensitive prostate cancer (HSPC) cells. Moreover, we found that CD51 was up-regulated in prostate cancer cells and promoted the carcinogenesis and progression of prostate cancer. However, the regulatory mechanism of SNHG17 and CD51 in the development of CRPC remains unclear. In the current study, we aimed to elucidate the expressions, functions, and underlying mechanism of SNHG17 and CD51 in CRPC. Our results further confirmed that both SNHG17 and CD51 were up-regulated in CRPC tissues and cells. In addition, we found that SNHG17 expression was positively correlated with CD51 expression in prostate cancer. Mechanically, SNHG17 functioned as a competing endogenous RNA (ceRNA) to up-regulate CD51 expression through competitively sponging microRNA-144 (miR-144), and CD51 was identified as a direct downstream target of miR-144 in CRPC. Functionally, down-regulation of SNHG17 or up-regulation of miR-144 inhibited the proliferation, migration, and invasion of CRPC cells, whereas up-regulation of SNHG17 and down-regulation of miR-144 promoted the proliferation, migration and invasion of CRPC cells in vitro and in vivo. Using gain and loss-of function assay and rescue assay, we showed that miR-144 inhibited cell proliferation, migration and invasion by directly inhibiting CD51 expression, and SNHG17 promoted cell proliferation, migration and invasion by directly enhancing CD51 expression in CRPC cells. Taken together, our study reveals the role of the SNHG17/miR-144/CD51 axis in accelerating CRPC cell proliferation and invasion, and suggests that SNHG17 may serve as a novel therapeutic target for CRPC.
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- 2020
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23. The anaphase promoting complex impacts repair choice by protecting ubiquitin signalling at DNA damage sites
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Kyungsoo Ha, Chengxian Ma, Han Lin, Lichun Tang, Zhusheng Lian, Fang Zhao, Ju-Mei Li, Bei Zhen, Huadong Pei, Suxia Han, Marcos Malumbres, Jianping Jin, Huan Chen, Yongxiang Zhao, Qing Zhu, and Pumin Zhang
- Subjects
Science - Abstract
The choice between homologous recombination and non-homologous end-joining is largely influenced by cell cycle. Here the authors show that APCCdh1 promotes homologous recombination by removing USP1, allowing polyubiquitinated histones to recruit BRCA1.
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- 2017
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24. Erratum: The anaphase promoting complex impacts repair choice by protecting ubiquitin signalling at DNA damage sites
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Kyungsoo Ha, Chengxian Ma, Han Lin, Lichun Tang, Zhusheng Lian, Fang Zhao, Ju-Mei Li, Bei Zhen, Huadong Pei, Suxia Han, Marcos Malumbres, Jianping Jin, Huan Chen, Yongxiang Zhao, Qing Zhu, and Pumin Zhang
- Subjects
Science - Abstract
Nature Communications 8: Article number: 15751 (2017); Published 12 June 2017; Updated 29 November 2017. This Article contains an error in Fig. 7. In Fig. 7b, the label ‘siBRCRA1’ should have read ‘si53BP1’. The correct version of the figure appears below as Fig. 1.
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- 2017
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25. Cancer Immunology and Cancer Immunodiagnosis
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Jianying Zhang, Suxia Han, Bin Zhang, and Yi Zhang
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Immunologic diseases. Allergy ,RC581-607 - Published
- 2014
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26. The Role of PAM4 in the Management of Pancreatic Cancer: Diagnosis, Radioimmunodetection, and Radioimmunotherapy
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Suxia Han, Guihua Jin, Lijuan Wang, Meng Li, Chenchen He, Xijing Guo, and Qing Zhu
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Immunologic diseases. Allergy ,RC581-607 - Abstract
PAM4, a new monoclonal antibody (MAb) known as clivatuzumab, is highly reactive with pancreatic cancer and precursor lesions. It is absent from the normal tissues and has limited reactivity with nonpancreatic cancer. The detailed characteristic of the PAM4 epitope is unknown but recent studies have shown that it is dependent on MUC1 glycosylation status. The limited PAM4 expression pattern makes it an attractive candidate for management of pancreatic adenocarcinoma. In addition, PAM4 is a serum biomarker for diagnosis of pancreatic cancer. Several different radiolabeled immunodiagnostic and immunotherapeutic agents of PAM4 have been developed and some are being evaluated in preclinical and/or clinical studies. The review will focus on PAM4 and its potential utility for the diagnosis, radioimmunodetection, and radioimmunotherapy of pancreatic cancer.
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- 2014
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27. Overexpression of YAP and TAZ is an independent predictor of prognosis in colorectal cancer and related to the proliferation and metastasis of colon cancer cells.
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Lijuan Wang, Shengjia Shi, Zhangyan Guo, Xiang Zhang, Suxia Han, Angang Yang, Weihong Wen, and Qing Zhu
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Medicine ,Science - Abstract
BACKGROUND AND OBJECTIVE: Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) are nuclear effectors of the Hippo pathway. Although they are abundantly expressed in the cytoplasm and nuclei of human colorectal cancer (CRC), and related to tumor proliferation status, there have been few studies on the predictive role of YAP and TAZ expression on the overall survival of patients with CRC. This study investigated YAP and TAZ expression in both CRC patients and colon cancer cell lines, and assessed their prognostic value. METHODS: Paraffin-embedded specimens from 168 eligible patients were used to investigate YAP and TAZ expression by immunohistochemistry, and compared with experimental results in colon cancer HCT116 cell line to explore their clinical significance in CRC. RESULTS: Statistically significant positive correlations were found between protein expression of YAP and TAZ in CRC tissues. Patients with higher YAP or TAZ expression showed a trend of shorter survival times; more importantly, our cohort study indicated that patients with both YAP and TAZ overexpression presented the worst outcomes. This was supported by multivariate analysis. In HCT116 colon cancer cells, the capacity for proliferation, metastasis, and invasion was dramatically reduced by knockdown of YAP and TAZ expressions by siRNA. CONCLUSIONS: Co-overexpression of YAP and TAZ is an independent predictor of prognosis for patients with CRC, and may account for the higher proliferation, metastasis, and poor survival outcome of these patients.
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- 2013
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28. Integrated Bioinformatics Analysis for Identificating the Therapeutic Targets of Aspirin in Small Cell Lung Cancer.
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Liuyun Gong, Dan Zhang, Yiping Dong, Yutiantian Lei, Yuanjie Qian, Xinyue Tan, Suxia Han, and Jiquan Wang
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- 2018
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29. SPOP promotes CDCA5 degradation to regulate prostate cancer progression via the AKT pathway
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Jinlu Ma, Yue Zhu, Jing Wang, Suxia Han, Yi Wang, Xiao Sun, Mengjiao Cai, Zhenzhen Luo, and Chenchen He
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Male ,Cancer Research ,Apoptosis ,Cell Cycle Proteins ,Review Article ,SPOP ,medicine.disease_cause ,CDCA5 ,medicine ,Biomarkers, Tumor ,Tumor Cells, Cultured ,Gene silencing ,Humans ,Protein kinase B ,PI3K/AKT/mTOR pathway ,RC254-282 ,Adaptor Proteins, Signal Transducing ,Cell Proliferation ,Ubiquitin degradation ,Prostate cancer ,biology ,Cell growth ,AKT ,Cell Cycle ,Ubiquitination ,Nuclear Proteins ,Prostatic Neoplasms ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Ubiquitin ligase ,Gene Expression Regulation, Neoplastic ,Repressor Proteins ,Essential gene ,Cancer cell ,Proteolysis ,biology.protein ,Cancer research ,Carcinogenesis ,Proto-Oncogene Proteins c-akt - Abstract
The E3 ubiquitin ligase adaptor Speckle-type POZ protein (SPOP) plays an important tumour suppressor role in prostate cancers (PCa), with mutation rate up to 15%. However, how SPOP mutations regulate prostate tumorigenesis remains elusive. Here, we report the identification of cell division cycle associated 5 (CDCA5) as a SPOP substrate. We found that SPOP interacts with CDCA5 and promotes its polyubiquitin degradation in a degron-dependent manner. This effect was greatly impaired by introducing PCa associated SPOP mutations. Importantly, we found that CDCA5 was essential for PCa cells to survive and proliferate. CDCA5 depletion in PCa cells led to cessation of proliferation, G2M arrest, severe sister chromatid aggregation disturbance, and apoptosis. we also found that CDCA5 knockdown decreased the protein expression of p-GSK3β, increased the activity of caspase-3, caspase-9, and the Bax/Bcl-2 ratio. Besides, we confirmed that CDCA5 interrupted cancer cell behavior via the AKT pathway. In contrast, silencing SPOP or overexpressing CDCA5 increased cell proliferation. Consistently, depleting SPOP along with CDCA5, or overexpressing CDCA5 along with SPOP also caused the growth of cells repressed. Consistent with the functional role of CDCA5, the mRNA and protein levels of CDCA5 were significantly increased in PCa, compared to normal tissues, and its high expression was associated with more severe lymph node metastasis, higher Gleason score, and poorer prognosis. Together, our data showed that SPOP plays a crucial role in inhibiting tumorigenesis and partly achieved this by promoting the degradation of oncoprotein CDCA5.
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- 2021
30. One Stone, Two Birds: A Peptide‐Au(I) Infinite Coordination Supermolecule for the Confederate Physical and Biological Radiosensitization in Cancer Radiation Therapy
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Jing Wang, Jing Zhao, Fang Ma, Liuyun Gong, Yinliang Lu, Weiping Xiao, Hanmin Tang, Chengyi Gao, Yuetong Chen, Jun Ma, Zhan Gao, Jin Yan, and Suxia Han
- Subjects
Biomaterials ,General Materials Science ,General Chemistry ,Biotechnology - Abstract
Over half of cancer patients are subjected to radiotherapy, but owing to the deficient amount of reactive oxygen radicals (ROS) and DNA double-strand breaks (DSBs), a fair number of them suffer from radiotherapy resistance and the subsequent short-term survival opportunity. To overcome it, many successes have been achieved in radiosensitizer discovery using physical strategy and/or biological strategy, but significant challenges remain regarding developing clinically translational radiosensitizers. Herein, a peptide-Au(I) infinite coordination supermolecule termed PAICS is developed that combined both physical and biological radiosensitization and possessed pharmaceutical characteristics including adequate circulatory stability, controllable drug release, tumor-prioritized accumulation, and the favorable body eliminability. As expected, monovalent gold ion endowed this supermolecule with high X-ray absorption and the subsequent radiosensitization. Furthermore, a peptide targeting CRM1, is assembled into the supermolecule, which successfully activates p53 and apoptosis pathway, thereby further sensitizing radiotherapy. As a result, PAICS showed superior ability for radiotherapy sensitization in vivo and maintained a favorable safety profile. Thus, the PAICS reported here will offer a feasible solution to simultaneously overcome both the pharmaceutical obstacles of physical and biological radiosensitizers and will enable the development of a class of nanomedicines for tumor radiotherapy sensitization.
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- 2022
31. Ubiquitin-specific protease 28 deubiquitinates TCF7L2 to govern the action of the Wnt signaling pathway in hepatic carcinoma
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Xiao Sun, Mengjiao Cai, Lingzhi Wu, Xinghua Zhen, Yuetong Chen, Jin Peng, Suxia Han, and Pumin Zhang
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Cancer Research ,Carcinoma, Hepatocellular ,F-Box-WD Repeat-Containing Protein 7 ,Deubiquitinating Enzymes ,Ubiquitin-Protein Ligases ,Liver Neoplasms ,General Medicine ,Oncology ,Cell Line, Tumor ,T Cell Transcription Factor 1 ,Humans ,Ubiquitin-Specific Proteases ,Transcription Factor 7-Like 2 Protein ,Ubiquitin Thiolesterase ,Wnt Signaling Pathway ,beta Catenin - Abstract
Overexpression of ubiquitin-specific protease 28 (USP28) is found in hepatic carcinoma. It is unclear whether the deubiquitinase plays a role in hepatocarcinogenesis. Deregulation of the Wnt signaling pathway is frequently associated with liver cancer. Transcription factor 7-like 2 (TCF7L2) is an important downstream transcription factor of the Wnt/β-catenin signaling pathway, but the mechanisms by which TCF7L2 itself is regulated have not yet been revealed. Here, we report that USP28 promotes the activity of the Wnt signaling pathway through maintaining the stability of TCF7L2. We further show that FBXW7 is the E3 ubiquitin ligase for TCF7L2. By regulating the levels of TCF7L2, USP28 modulates the Wnt/β-catenin signaling in liver cancer and USP28 depletion or inhibition by a small molecule inhibitor leads to a halt of growth in liver cancer cells. These results suggest that USP28 could be a potential therapeutic target for liver cancer.
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- 2022
32. Engineering of Gold Nanorods as Multifunctional Theranostic Agent for Photothermal-Enhanced Radiotherapy of Cervical Cancer
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Lina Xie, Xia Ying, Xinyue Li, Xinyue Tan, Tianzi Zhang, Xujia Zhang, Wen Cai, Feifei An, Xiaoli Liu, and Suxia Han
- Abstract
Radiotherapy (RT) is an important method in the treatment of cervical cancer. Devising exceedingly effective, conveniently synthesizable, and lowly poisonous smart multifunctional radiosensitizers is of tremendous significance to improve the cure rate of RT. Gold nanorods (GNRs), which exhibited dramatic X-ray absorption and near-infrared (NIR) photothermal conversion effectiveness, could be utilized as radiosensitizers. In the present study, an all-in-one theranostic nanoagent for photothermal-enhanced radiotherapy of carcinoma was devised based on GNRs with aggregation-induced emission (AIE) attributes (NPAPF-GNRs@PEG). NPAPF-GNRs@PEG-mediated PTT-RT demonstrated excellent radiation sensitization effect by significantly inhibiting invasion and migration, increasing ROS and causing more DNA damage in two different pathological types of cell lines of cervical cancer. Experiments of in vitro and in vivo and metabolomics study demonstrated that PTT-RT based on NPAPF-GNRs@PEG showed enhanced RT effect by increasing apoptosis, compared to RT alone. Meanwhile, the NPAPF-GNRs@PEG nanoagent exhibited excellent tomography imaging (CTI)/photoacoustic imaging (PAI)/fluorescence imaging (FLI)/photothermal imaging (PTI) multi-modal imaging in vitro and in vivo. Therefore, the present study provides an innovative multifunctional platform for optimizing the curative efficacy of precision RT and further enriches the theoretical basis of the mechanistic study of radio-sensitization by GNRs-mediated PTT-RT.
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- 2022
33. Application of Radiosensitizers in Cancer Radiotherapy
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Chengcheng Liu, Mingzhen Zhang, Liuyun Gong, Suxia Han, and Yujie Zhang
- Subjects
Radiation-Sensitizing Agents ,medicine.medical_treatment ,Biophysics ,Normal tissue ,mechanism ,Pharmaceutical Science ,Antineoplastic Agents ,Bioengineering ,Healthy tissue ,Review ,02 engineering and technology ,010402 general chemistry ,01 natural sciences ,Biomaterials ,Neoplasms ,Drug Discovery ,therapeutics ,High doses ,medicine ,cancer radiotherapy ,Animals ,Humans ,Radiotherapy ,Low toxicity ,business.industry ,Organic Chemistry ,General Medicine ,021001 nanoscience & nanotechnology ,nanomedicine ,0104 chemical sciences ,Cancer treatment ,Radiation therapy ,Cancer Radiotherapy ,Cancer cell ,Cancer research ,radiosensitizers ,0210 nano-technology ,business - Abstract
Radiotherapy (RT) is a cancer treatment that uses high doses of radiation to kill cancer cells and shrink tumors. Although great success has been achieved on radiotherapy, there is still an intractable challenge to enhance radiation damage to tumor tissue and reduce side effects to healthy tissue. Radiosensitizers are chemicals or pharmaceutical agents that can enhance the killing effect on tumor cells by accelerating DNA damage and producing free radicals indirectly. In most cases, radiosensitizers have less effect on normal tissues. In recent years, several strategies have been exploited to develop radiosensitizers that are highly effective and have low toxicity. In this review, we first summarized the applications of radiosensitizers including small molecules, macromolecules, and nanomaterials, especially those that have been used in clinical trials. Second, the development states of radiosensitizers and the possible mechanisms to improve radiosensitizers sensibility are reviewed. Third, the challenges and prospects for clinical translation of radiosensitizers in oncotherapy are presented.
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- 2021
34. Tamoxifen induces fatty liver disease in breast cancer through the MAPK8/FoxO pathway
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Yutiantian Lei, Xiao Sun, Zhenzhen Luo, Hanmin Tang, Jinlu Ma, Lina Xie, Suxia Han, Mengjiao Cai, Liuyun Gong, Xinyue Tan, and Chenchen He
- Subjects
0301 basic medicine ,bioinformatics analysis ,MAPK8 ,Medicine (miscellaneous) ,Estrogen receptor ,Biology ,03 medical and health sciences ,breast cancer ,0302 clinical medicine ,Breast cancer ,medicine ,KEGG ,skin and connective tissue diseases ,Protein kinase A ,Research Articles ,fatty liver ,lcsh:R5-920 ,fungi ,Fatty liver ,medicine.disease ,030104 developmental biology ,TAM ,030220 oncology & carcinogenesis ,Cancer research ,Molecular Medicine ,Signal transduction ,lcsh:Medicine (General) ,Tamoxifen ,Research Article ,FoxO signaling pathway ,medicine.drug - Abstract
Background Prevention of metabolic complications of long‐term adjuvant endocrine therapy in breast cancers remained a challenge. We aimed to investigate the molecular mechanism in the development of tamoxifen (TAM)‐induced fatty liver in both estrogen receptor (ER)‐positive and ER‐negative breast cancer. Methods and results First, the direct protein targets (DPTs) of TAM were identified using DrugBank5.1.7. We found that mitogen‐activated protein kinase 8 (MAPK8) was one DPT of TAM. We identified significant genes in breast cancer and fatty liver disease (FLD) using the MalaCards human disease database. Next, we analyzed the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of those significant genes in breast cancer and FLD using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING). We found that overlapping KEGG pathways in these two diseases were MAPK signaling pathway, Forkhead box O (FoxO) signaling pathway, HIF‐1 signaling pathway, AGE‐RAGE signaling pathway in diabetic complications, and PI3K‐Akt signaling pathway. Furthermore, the KEGG Mapper showed that the MAPK signaling pathway was related to the FoxO signaling pathway. Finally, the functional relevance of breast cancer and TAM‐induced FLD was validated by Western blot analysis. We verified that TAM may induce fatty liver in breast cancer through the MAPK8/FoxO signaling pathway. Conclusion Bioinformatics analysis combined with conventional experiments may improve our understanding of the molecular mechanisms underlying side effects of cancer drugs, thereby making this method a new paradigm for guiding future studies on this issue.
- Published
- 2020
35. Effect of miR-196a inhibition on esophageal cancer growth in vitro
- Author
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Minghua Bai, Xiao Sun, Suxia Han, Congya Zhou, Yiping Dong, and Jinlu Ma
- Subjects
0301 basic medicine ,Cancer Research ,Esophageal Neoplasms ,medicine.medical_treatment ,Apoptosis ,In Vitro Techniques ,Targeted therapy ,03 medical and health sciences ,0302 clinical medicine ,Biomarkers, Tumor ,Tumor Cells, Cultured ,Humans ,Medicine ,Pyrroles ,Pharmacology (medical) ,Protein Kinase C ,Protein kinase C ,Cell Proliferation ,Pharmacology ,Gene knockdown ,biology ,business.industry ,Kinase ,Cell growth ,Esophageal cancer ,medicine.disease ,Proliferating cell nuclear antigen ,Gene Expression Regulation, Neoplastic ,MicroRNAs ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Quinazolines ,Cancer research ,biology.protein ,business - Abstract
Esophageal cancer has recent shown a higher incidence but lower 5-year survival rate after normal clinical treatment in China. The aim of this study was to observe whether the inhibition of miR-196a affects esophageal cancer cell growth by modulating the nuclear factor-κB target gene and to detect the possible cooperative therapeutic effects on esophageal cancer by knocking down miR-196a expression combined with the specific inhibitor of nuclear factor-κB target genes. Thus, anti-miR-196a or sotrastaurin, a protein kinase C (PKC) inhibitor, were used to alter PKC expression. We found that miR-196a knockdown or PKC inhibition by sotrastaurin changed PKC expression which then reduced esophageal cancer cell proliferation and downregulated proliferating cell nuclear antigen expression via the classical B-cell receptor-PKC nuclear factor-κB pathway but not the alternative pathway; in addition, miR-196a inhibition can increase the caspase level and induce esophageal cancer cell apoptosis. Our current results provided the evidence that miR-196a was related to the classical nuclear factor-κB pathway, and these new findings proved the potential therapeutic effect of miR-196a in targeted therapy for clinical esophageal cancer patients.
- Published
- 2020
36. The deubiquitinase USP28 stabilizes the expression of RecQ family helicases and maintains the viability of triple negative breast cancer cells
- Author
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Xinghua Zhen, Suxia Han, Lichun Tang, Yiping Dong, Lingzhi Wu, Jin Peng, Jiewei Wang, Huailu Ma, Pumin Zhang, and Jianping Jin
- Subjects
BLM, bloom syndrome gene product ,Cell Survival ,RecQ helicase ,WRN, werner syndrome gene product ,Estrogen receptor ,Triple Negative Breast Neoplasms ,Biochemistry ,USP28 ,TNBC, triple-negative breast cancer ,chemistry.chemical_compound ,Breast cancer ,Cell Line, Tumor ,Progesterone receptor ,medicine ,Humans ,Propidium iodide ,Molecular Biology ,Triple-negative breast cancer ,Cell Proliferation ,biology ,RECQL5 ,Deubiquitinating Enzymes ,RecQ Helicases ,USP, Ubiquitin-specific cysteine protease ,Helicase ,Cell Biology ,G2-M DNA damage checkpoint ,medicine.disease ,DUB, deubiquitin enzyme ,deubiquitinase ,chemistry ,Cancer research ,biology.protein ,triple-negative breast cancer ,RecQ family helicases ,Ubiquitin Thiolesterase ,Research Article - Abstract
Triple-negative breast cancer lacks significant expression of the estrogen receptor, the progesterone receptor, and of human epidermal growth factor receptor. It is the most aggressive and malignant of all breast cancers, and for which there are currently no effective targeted therapies. We have shown previously that the RecQ helicase family member RECQL5 is essential for the proliferation and survival of TNBC cells; however, the mechanism of its involvement in cell viability has not been shown. Here we report that the expression of RecQ family helicases, including RECQL5, are regulated by the deubiquitinase USP28. We found using genetic depletion or a small molecule inhibitor that like RECQL5, USP28 is also essential for TNBC cells to proliferate in vitro and in vivo. Compromising the function of USP28 by shRNA knockdown or the inhibitor caused TNBC cells to arrest in S/G2 phases, concurrent with DNA damage checkpoint activation. We further showed that the small molecule inhibitor of USP28 displayed anti-tumor activity against xenografts derived from TNBC cells. Our results suggest that USP28 could be a potential therapeutic target for triple negative breast cancer.
- Published
- 2021
37. [c-Ski improves beagle atrial structural remodeling by suppressing TGF-β1-SMAD signaling and p38 MAPK pathway]
- Author
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Suxia, Han, Juan, Wang, Suli, Gao, Lezhi, Sheng, and Yao, Li
- Subjects
DNA-Binding Proteins ,Transforming Growth Factor beta1 ,Dogs ,Proto-Oncogene Proteins ,Animals ,Humans ,Heart Atria ,Fibrosis ,p38 Mitogen-Activated Protein Kinases ,Signal Transduction - Abstract
Objective To investigate the role and mechanism of c-Ski in atrial structural remodeling by rapid atrial pacing in a canine model. Methods The expression levels of c-Ski, α-smooth muscle actin (α-SMA) and type III collagen (Col3) in atrial tissues of patients with atrial fibrillation (AF) and their correlations were detected by real time quantitative PCR and Pearson's correlation analysis. A canine atrial rapid pacing model was constructed. The expression and distribution of α-SMA and Col3 were detected by immunohistochemical staining. The levels of inflammatory cytokines interleukin-18 (IL-18) and Toll-like receptor 4 (TLR4) in serum and atrial tissues were determined by ELISA. The regulation effect of c-Ski on α-SMA, Col3, transforming growth factor β1 (TGF-β1)/SMAD pathway and p38 MAPK pathway were overexpressed and detected by Western blotting. Results c-Ski expression was down-regulated in the atrial tissues of AF patients, and showed a negative correlation with the expression of α-SMA and Col3 in AF. In addition, c-Ski expression showed a down-regulation in the canine atrial rapid pacing model. Overexpression of c-Ski significantly inhibited α-SMA and Col3 levels, as well as levels of inflammatory cytokines IL-18 and TLR4 in serum and atrial tissues, and alleviated AF induced atrial fibrosis by inhibiting TGF-β1-Smad pathway and p38 MAPK pathway in the canine atrial rapid pacing model. Conclusion Overexpression of c-Ski can improve atrial structural remodeling induced by rapid pacing by inhibiting TGF-β1-SMAD pathway and p38 MAPK pathway.
- Published
- 2021
38. All‐In‐One Biomimetic Nanoplatform Based on Hollow Polydopamine Nanoparticles for Synergistically Enhanced Radiotherapy of Colon Cancer
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Liuyun Gong, Yujie Zhang, Jing Zhao, Yilei Zhang, Kangsheng Tu, Lianying Jiao, Qiuran Xu, Mingzhen Zhang, and Suxia Han
- Subjects
Indoles ,Polymers ,General Chemistry ,Biomaterials ,Photochemotherapy ,Biomimetics ,Cell Line, Tumor ,Colonic Neoplasms ,Tumor Microenvironment ,Humans ,Nanoparticles ,General Materials Science ,Hypoxia ,Biotechnology - Abstract
Even though radiotherapy is the most important therapeutic strategy for colon cancer treatment, there is an enormous demand to improve radiosensitivity in solid tumor destruction. For this purpose, a biomimetic nanoplatform based on hollow polydopamine nanoparticles (HP) with homologous targeting and pH-responsive drug release properties is designed. In this work, HP is constructed by using a chelation competition-induced polymerization strategy and then modified with the cancer cell membrane. Hollow polydopamine integrated with Pt nanoparticles (Pt@HP) has a catalase-like activity, which can be used to trigger endogenous H
- Published
- 2022
39. The Deubiquitin Enzyme USP28 Maintains the Viability of Triple Negative Breast Cancer Cells through Stabilizing the RecQ Family Helicases
- Author
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Lingzhi Wu, Yiping Dong, Jiewei Wang, Lichun Tang, Jianping Jin, Xinghua Zhen, Huailu Ma, Suxia Han, Pumin Zhang, and Jin Peng
- Subjects
chemistry.chemical_classification ,Text mining ,Enzyme ,chemistry ,business.industry ,Cancer research ,biology.protein ,Helicase ,Biology ,business ,Triple-negative breast cancer - Abstract
Background: Triple-negative breast cancer lacks significant expression of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. It is the more aggressive and malignant kind of breast cancers and is currently without any effective targeted therapies.Methods: We have screened for genes in the ubiquitin-proteasome system that are essential for the proliferation and survival of TNBC cells via CRISPR/Cas9-mediated gene editing. Growth of TNBC cells were assayed using cell and tumor xenograft models to validate the vital role of USP28. We employed cell biology and biochemical methods to uncover the mechanisms underlying the requirement of USP28 for the proliferation of TNBC cells.Results: USP28, a deubiquitin enzyme, is an essential gene for TNBC cells in vitro and in vivo. Compromising the function of USP28 causes TNBC cells to arrest in S/G2 phases with DNA damage checkpoint activation. We show that RecQ family helicases are regulated by USP28, which is more important in TNBC cells than in other breast cancer cells. We further showed that a small molecule inhibitor of USP28 displayed anti-tumor activities against xenografts derived from TNBC cells.Conclusion: Our data establish a critical role played by USP28 in supporting the proliferation and viability of triple negative breast cancer cells through stabilizing RecQ family helicases and support USP28 as a therapeutic target for TNBC.
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- 2021
40. The SPOP-ITCH Signaling Axis Protects Against Prostate Cancer Metastasis
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Bo Xu, Yaqi Mo, Yuan Ma, Jie Chen, Mengjiao Cai, Suxia Han, Joshua Fried, Jinlu Ma, and Xinyue Tan
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0301 basic medicine ,Cancer Research ,SPOP ,medicine.disease_cause ,Metastasis ,Causes of cancer ,03 medical and health sciences ,Prostate cancer ,0302 clinical medicine ,Ubiquitin ,medicine ,metastasis ,ubiquitylation ,RC254-282 ,Original Research ,Gene knockdown ,Mutation ,biology ,business.industry ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,prostate cancer ,ITCH ,Ubiquitin ligase ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,biology.protein ,Cancer research ,business - Abstract
Prostate cancer is one of the most common causes of cancer incidence and death in men, with the mortality caused primarily by the late-stage and metastatic forms of the disease. The mechanisms and molecular markers for prostate cancer metastasis are not fully understood. Speckle type Poz Protein (SPOP) is an E3 ubiquitin ligase adaptor that is often mutated in prostate cancer. In this study, we sequenced the SPOP gene in 198 prostate cancer patients and found 16 mutations in the cohort. Multivariate analysis revealed that SPOP mutations correlated with the clinical stage of the disease and strongly with metastasis. We identified ITCH as a candidate protein for SPOP-mediated degradation via mass spectrometry. We demonstrated the interaction between SPOP and ITCH, and found that the SPOP F133L mutation disrupted the SPOP-ITCH interaction, leading to a subsequent increase in the ITCH protein level. Further, we found that the SPOP knockdown led to higher levels of Epithelial- mesenchymal transition (EMT) proteins and increased cell invasion. Together, our results highlight the functional significance of the SPOP-ITCH pathway in prostate cancer metastasis.
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- 2021
41. Promethazine inhibits proliferation and promotes apoptosis in colorectal cancer cells by suppressing the PI3K/AKT pathway
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Jiahao Sun, Xinyue Tan, Jie Chen, Liuyun Gong, Suxia Han, Xinyue Li, Lina Xie, Qi Wang, Xinyue Zhang, and Xuehui Luo
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colorectal cancer ,Antineoplastic Agents ,Apoptosis ,RM1-950 ,Promethazine ,Flow cytometry ,Databases, Genetic ,medicine ,Humans ,KEGG ,Protein kinase B ,PI3K/AKT/mTOR pathway ,Cell Proliferation ,Pharmacology ,drug repurposing ,medicine.diagnostic_test ,Chemistry ,Akt/PKB signaling pathway ,Drug Repositioning ,General Medicine ,HCT116 Cells ,Mitochondria ,PI3K/AKT pathway ,Blot ,Gene Expression Regulation, Neoplastic ,Cancer research ,Phosphorylation ,Therapeutics. Pharmacology ,Caco-2 Cells ,Phosphatidylinositol 3-Kinase ,Apoptosis Regulatory Proteins ,Colorectal Neoplasms ,HT29 Cells ,Proto-Oncogene Proteins c-akt ,Signal Transduction - Abstract
Aim To elucidate the potential effect of promethazine on colorectal cancer (CRC) cells and the underlying mechanism. Materials and methods Targets of the drug promethazine (PMTZ) were identified by DrugBank and comparative toxicogenomic databases (CTD), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was performed with STRING software. The effects of PMTZ were predicted to be associated with the PI3K/AKT pathway. Cell Counting Kit 8 (CCK-8) assays were used to evaluate the effects of different concentrations of PMTZ on the proliferation of various types of CRC cells. Flow cytometry and Western blotting analyses were used to detect the degree of CRC cell apoptosis and the expression of the apoptosis-related proteins Bcl-2, Bax and caspase-3 after PMTZ treatment. The expression levels of PI3K/AKT pathway-related proteins [PI3K, AKT, phosphorylated (P)-PI3K and p-AKT] in CRC cells treated with PMTZ were analyzed by Western blotting. Results PMTZ inhibited the proliferation and promoted the apoptosis of CRC cells and suppressed the activation of the PI3K/AKT signaling pathway in a dose-dependent manner. Discussion and conclusions PMTZ may suppress the proliferation and induce the apoptosis of CRC cells by inhibiting the PI3K/ AKT signaling pathway. This study reported, for the first time, the function of PMTZ in CRC cells and the underlying mechanism and further confirmed the potential antitumor effects of phenothiazine. The combination of bioinformatics analyses and experiments provides informative evidence for the reuse of drugs and the development of new drugs.
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- 2021
42. Propranolol selectively inhibits cervical cancer cell growth by suppressing the cGMP/PKG pathway
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Dan Zhang, Xinyue Tan, Yiping Dong, Zhenzhen Luo, Yutiantian Lei, Liuyun Gong, and Suxia Han
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0301 basic medicine ,Bioinformatical analysis ,Proliferation ,Uterine Cervical Neoplasms ,Apoptosis ,RM1-950 ,Flow cytometry ,03 medical and health sciences ,0302 clinical medicine ,Cell Line, Tumor ,Cyclic GMP-Dependent Protein Kinases ,medicine ,Humans ,MTT assay ,Protein Interaction Maps ,KEGG ,Cyclic GMP ,Cell Proliferation ,Pharmacology ,medicine.diagnostic_test ,GMP biosynthetic process ,Cell growth ,Chemistry ,General Medicine ,Propranolol ,Blot ,030104 developmental biology ,030220 oncology & carcinogenesis ,Cancer research ,Cervical cancer ,Female ,Therapeutics. Pharmacology ,Function (biology) ,cGMP-PKG signaling pathway ,HeLa Cells ,Signal Transduction - Abstract
Aim To observe the effect of propranolol in cervical cancer and investigate the mechanism of the effect. Methods and Results We found 5 direct protein targets (DPTs) of propranolol (PRO) by DrugBank5.0 firstly. Next, we analyzed protein-protein interaction (PPI) network and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of PRO DPTs and the result showed that PRO was linked with cGMP/PKG pathway. Then, we recognized the top 38 upexpressed genes of cervical cancer (CC) based original microarray datasets (GSE7803, GSE9750, GSE39001 and GSE63514). Further, we analyzed the biological process with the 38 overexpressed genes by STRING. We found some of overexpressed genes of CC participated in GMP biosynthetic process. Lastly, the function of PRO in CC was validated by MTT assay, Western blotting, flow cytometry and colony formation assay methods. We verified PRO can suppress cGMP/PKG pathway then inhibits CC cell growth. Conclusion The bioinformatical analysis combine with traditional experiment can help us understanding potential molecular mechanism about how PRO acting in CC. This method is a new paradigm which can guide future researches about mechanism in existing diseases and drugs.
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- 2019
43. Alternol eliminates excessive ATP production by disturbing Krebs cycle in prostate cancer
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Partha Krishnamurthy, Haixia Xu, Yuzhe Tang, Suxia Han, Changlin Li, Hemantkumar Chavan, Antonio Artigues, Shaofeng Duan, Marcus Laird Forrest, Ying Xu, Jeffrey M. Holzbeierlein, Benyi Li, and Chenchen He
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Male ,0301 basic medicine ,Urology ,Citric Acid Cycle ,Antineoplastic Agents ,Apoptosis ,Mitochondrion ,Heterocyclic Compounds, 4 or More Rings ,Article ,03 medical and health sciences ,Prostate cancer ,Adenosine Triphosphate ,0302 clinical medicine ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Cell Proliferation ,Chemistry ,Prostate ,Prostatic Neoplasms ,Cancer ,Pyruvate dehydrogenase complex ,medicine.disease ,Mitochondria ,Citric acid cycle ,030104 developmental biology ,Oncology ,Biochemistry ,Cell culture ,030220 oncology & carcinogenesis ,Fumarase ,Cancer cell ,Drug Screening Assays, Antitumor - Abstract
Background Alternol is a natural compound isolated from fermentation products of a mutant fungus. Our previous studies demonstrated that Alternol specifically kills cancer cells but spares benign cells. Methods To investigate the mechanism underlying alternol-induced cancer cell-specific killing effect, we took a comprehensive strategy to identify Alternol's protein targets in prostate cancer cells, including PC-3, C4-2, and 22RV1, plus benign BPH1 cell lines. Major experimental techniques included biotin-streptavidin pulldown assay coupled with mass-spectrometry, in vitro enzyme activity assay for Krebs cycle enzymes and gas chromatography-mass spectrometry (GC-MS) for metabolomic analysis. Results Among 14 verified protein targets, four were Krebs cycle enzymes, fumarate hydratase (FH), malate dehydrogenase-2 (MDH2), dihydrolipoamide acetyltransferase (DLAT) in pyruvate dehydrogenase complex (PDHC) and dihydrolipoamide S-succinyltransferase (DLST) in a-ketoglutarate dehydrogenase complex (KGDHC). Functional assays revealed that PDHC and KGDHC activities at the basal level were significantly higher in prostate cancer cells compared to benign prostate BPH1 cells, while alternol treatment reduced their activities in cancer cells close to the levels in BPH1 cells. Although FH and MDH2 activities were comparable among prostate cancer and benign cell lines at the basal level, Alternol treatment largely increased their activities in cancer cells. Metabolomic analysis revealed that Alternol treatment remarkably reduced the levels of malic acid, fumaric acid, and isocitric acid and mitochondrial respiration in prostate cancer cells. Alternol also drastically reduced mitochondrial respiration and ATP production in PC-3 cells in vitro or in xenograft tissues but not in BPH1 cells or host liver tissues. Conclusions Alternol interacts with multiple Krebs cycle enzymes, resulting in reduced mitochondrial respiration and ATP production in prostate cancer cells and xenograft tissues, providing a novel therapeutic strategy for prostate cancer treatment.
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- 2019
44. Application of Radiosensitizers in Cancer Radiotherapy [Corrigendum]
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Liuyun Gong, Yujie Zhang, Chengcheng Liu, Mingzhen Zhang, and Suxia Han
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Biomaterials ,International Journal of Nanomedicine ,Organic Chemistry ,Drug Discovery ,Biophysics ,Pharmaceutical Science ,Bioengineering ,General Medicine ,Corrigendum - Abstract
Gong L, Zhang Y, Liu C, Zhang M, Han S. Int J Nanomedicine. 2021;16:1083–1102. The authors have advised there is an error with the reference list on page 1100. Reference 160 should read as follows. 160. Gong LJ, Xie JN, Zhu S, Gu ZJ, Zhao YL. Application of multifunctional nanomaterials in tumor radiosensitization. Acta Phys Chim Sin. 2018;34(2):140–167. doi.org/10.3866/PKU.WHXB201707174 The updated reference should have also been cited in the additional following places: Page 1092, Heavy Metal Nanomaterials section, second sentence, the text should read “Based on this, numerous studies have focused on these heavy metal nanomaterials to investigate their radiotherapy sensitization.160” Page 1094, Nonmetallic Nanomaterials section, second sentence, the text should read “For example, C60, fullerene, has potent anticancer activities, however, the potential toxicity to normal tissues limits its further use.160” The authors apologize for these errors. Read the original article
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- 2021
45. Transcriptome-wide association study identifies multiple genes and pathways associated with pancreatic cancer
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Xinyue Tan, Yuanjie Qian, Liuyun Gong, Yutiantian Lei, Suxia Han, and Dan Zhang
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0301 basic medicine ,Cancer Research ,Candidate gene ,pancreatic cancer ,Genome-wide association study ,Single-nucleotide polymorphism ,Computational biology ,Biology ,Polymorphism, Single Nucleotide ,Transcriptome ,03 medical and health sciences ,transcriptome‐wide association study ,0302 clinical medicine ,Pancreatic cancer ,Biomarkers, Tumor ,medicine ,Humans ,Gene Regulatory Networks ,Genetic Predisposition to Disease ,Radiology, Nuclear Medicine and imaging ,Gene ,Original Research ,Cancer Biology ,genome‐wide association study ,Gene Expression Profiling ,Cell cycle ,medicine.disease ,Gene Expression Regulation, Neoplastic ,Pancreatic Neoplasms ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,Female ,Pancreas ,Software ,Genome-Wide Association Study - Abstract
Aim To identify novel candidate genes for pancreatic cancer. Methods We performed a transcriptome-wide association study (TWAS) analysis of pancreatic cancer (PC). GWAS summary data were driven from the published studies of PC, totally involving 558 542 SNPs in 1896 individuals with pancreatic cancer and 1939 healthy controls. FUSION software was applied to the PC GWAS summary data for tissue-related TWAS analysis, including whole blood, peripheral blood, adipose, and pancreas. The functional relevance of identified genes with PC was further validated by Oncomine, STRING, and CluePedia tool. Results Transcriptome-wide association study analysis identified 19 genes significantly associated with PC, such as LRP5L (P value = 5.21 × 10-5 ), SOX4 (P value = 3.2 × 10-4 ), and EGLN3 (P value = 6.2 × 10-3 ). KEGG pathway enrichment analysis detected several PC-associated pathways, such as One carbon pool by folate (P value = 1.60 × 10-16 ), Cell cycle (P value = 1.27 × 10-7 ), TGF-beta signaling pathway (P value = 4.64 × 10-6 ). Further comparing the 19 genes with previously identified overexpressed genes in PC patients found one overlapped gene SOX4. Conclusion We identified some novel candidate genes and pathways associated with PC. Our results provide novel clues for the genetic mechanism studies of pancreatic cancer.
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- 2018
46. Identifying chemicals linked to lung cancer: Integrating genome-wide association studies with a chemical-gene interaction network
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Yutiantian Lei, Hanmin Tang, Liuyun Gong, Zhenzhen Luo, Xinyue Tan, Lina Xie, Chenchen He, Jinlu Ma, and Suxia Han
- Abstract
Background Lung cancer is the most common cancer and the leading cause of cancer-related mortality worldwide. Environmental chemicals play a significant role in tumorigenesis, it is necessary to explore the lung cancer-related chemicals and provide new clues for neoplastic prevention and treatment. Methods The genome-wide association study (GWAS) summary data of malignant neoplasm of bronchus and lung (C34) were downloaded from the UK Biobank. It includes 1,655 samples and 450,609 controls. DNA methylation profiles of non-small cell lung cancer were obtained from the GEO database (GSE75008). A transcriptome-wide association study was applied to detect genes significantly related to lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD) by FUSION software. Comparative toxicogenomics database (CTD) enables the construction of chemical-gene-disease networks. We conducted a chemical-related gene set enrichment analysis (GSEA) based on GWAS summary data, DNA methylation data, and the CTD to explore the relationships between chemicals and two major histological subtypes of lung cancer. Venn analysis was used to identify the common related chemicals of the GWAS summary data and the DNA methylation data. Results We detected aluminum, naringenin, and 2-acetylaminofluorene as LUSC-related chemicals and antirheumatic agents, nickel monoxide, and 2-amino-2-methyl-1-propanol as LUAD-related chemicals. Conclusion By integrating GWAS and chemical-gene interaction networks, we made linkages between various chemicals and lung cancer on genetic basis. Moreover, this study provided new clues for exploring the etiology of lung cancer and a new method for finding the chemicals related to tumor or other complex disease.
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- 2020
47. Integrative, genome-wide association study identifies chemicals associated with common women's malignancies
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Lina Xie, Zhenzhen Luo, Suxia Han, Jinlu Ma, Hanmin Tang, Yutiantian Lei, Liuyun Gong, Chenchen He, and Xinyue Tan
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0106 biological sciences ,Oncology ,medicine.medical_specialty ,Methylnitronitrosoguanidine ,Parabens ,Uterine Cervical Neoplasms ,Genome-wide association study ,Breast Neoplasms ,Biology ,Quinolones ,01 natural sciences ,03 medical and health sciences ,Breast cancer ,Fenofibrate ,Phenols ,Internal medicine ,Genetics ,medicine ,Humans ,030304 developmental biology ,Cervical cancer ,Ovarian Neoplasms ,0303 health sciences ,Cancer prevention ,Gene Expression Profiling ,Incidence ,Cancer ,Environmental Exposure ,medicine.disease ,Biobank ,Female ,Toxicogenomics ,Ovarian cancer ,Glafenine ,010606 plant biology & botany ,Genome-Wide Association Study - Abstract
Background Breast cancer, cervical cancer, and ovarian cancer are three of the most commonly diagnosed malignancies in women, and more cancer prevention research is urgently needed. Methods Summary data of a large genome-wide association study of female cancers were derived from the UK biobank. We performed a transcriptome-wide association study and a gene set enrichment analysis to identify correlations between chemical exposure and aberrant expression, repression, or mutation of genes related to cancer using the Comparative Toxicogenomics Database. Results We identified five chemicals (NSC668394, glafenine, methylnitronitrosoguanidine, fenofibrate, and methylparaben) that were associated with the incidence of both breast cancer and cervical cancer. Conclusion Using a transcriptome-wide association study and gene set enrichment analysis we identified environmental chemicals that are associated with an increased risk of breast cancer, cervical cancer, and ovarian cancer.
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- 2020
48. Circular RNA hsa_circ_0009172 suppresses gastric cancer by regulation of microRNA-485-3p-mediated NTRK3
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Hao Wang, Nan Wang, Xue Li, Xiaoli Zheng, Ke Ye, Suxia Han, Lei Wu, and Chengcheng Fan
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0301 basic medicine ,Cancer Research ,Mice, Nude ,Transfection ,Metastasis ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Circular RNA ,Stomach Neoplasms ,Cell Line, Tumor ,microRNA ,medicine ,Animals ,Humans ,Luciferase ,Receptor, trkC ,Molecular Biology ,Cell Proliferation ,Chemistry ,RNA ,Cancer ,RNA, Circular ,medicine.disease ,In vitro ,030104 developmental biology ,030220 oncology & carcinogenesis ,Cancer cell ,Cancer research ,Molecular Medicine - Abstract
Gastric cancer is the third leading cause of cancer-related death worldwide, with relapse and metastasis being major contributors to the mortality. Circular RNAs (circRNAs) have been at the center of several researches and some circRNAs have been indicated to be involved in gastric cancer as sponges. Nevertheless, the mechanism underlying the function of circRNA remains largely unclear. Therefore, this study was conducted with the main objective of screening the associated circRNA in gastric cancer and exploring its mechanism. Expression of hsa_circRNA_0009172 was validated in gastric cancer tissues and cell lines after the correlation between hsa_circRNA_0009172 and prognosis was determined. Moreover, the binding site between miR-485-3p and hsa_circRNA_0009172 or NTRK3 was verified using dual luciferase assay and RNA pull down. Function-gain and -loss experiments were performed for the purpose of detecting the effect of hsa_circRNA_0009172 in vivo and in vitro as well as its mechanism with microRNA (miRNA)-485-3p and NTRK3 in gastric cancer. The hsa_circRNA_0009172 expression was downregulated in gastric cancer tissues and cell lines, indicating a positive association with patient prognosis. Functionally, hsa_circ_0009172 overexpression inhibited proliferative, invasive and migrative potential of gastric cancer cells as well as epithelial-mesenchymal transition (EMT)-related proteins by sponging miR-485-3p to inhibit NTRK3, while miR-485-3p overexpression could reverse the inhibitory effect of hsa_circ_0009172 on gastric cancer. Furthermore, either up-regulation of hsa_circ_0009172 or down-regulation of miR-485-3p led to the suppression of xenograft tumor growth in nude mice. In conclusion, hsa_circ_0009172 serves as a tumor suppressor in gastric cancer by targeting miR-485-3p/NTRK3 axis.
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- 2020
49. Integrating Genome-Wide Association Studies and Gene Expression Profiles With Chemical-Genes Interaction Networks to Identify Chemicals Associated With Colorectal Cancer
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Suxia Han, Hanmin Tang, Chenchen He, Jinlu Ma, Lina Xie, Yutiantian Lei, Xinyue Tan, Zhenzhen Luo, and Liuyun Gong
- Subjects
gene set enrichment analysis ,0301 basic medicine ,Importazole ,lcsh:QH426-470 ,Colorectal cancer ,colorectal cancer ,Genome-wide association study ,Computational biology ,Biology ,03 medical and health sciences ,0302 clinical medicine ,Gene expression ,medicine ,Genetics ,Gene ,Genetics (clinical) ,Original Research ,genome-wide association study ,Cancer ,medicine.disease ,Biobank ,comparative toxicogenomics database ,digestive system diseases ,transcriptome-wide association study ,lcsh:Genetics ,030104 developmental biology ,030220 oncology & carcinogenesis ,Molecular Medicine ,Toxicogenomics - Abstract
Colorectal cancer (CRC) is the third most common cancer and has the second highest mortality rate in global cancer. Exploring the associations between chemicals and CRC has great significance in prophylaxis and therapy of tumor diseases. This study aims to explore the relationships between CRC and environmental chemicals on genetic basis by bioinformatics analysis. The genome-wide association study (GWAS) datasets for CRC were obtained from the UK Biobank. The GWAS data for colon cancer (category C18) includes 2,581 individuals and 449,683 controls, while that of rectal cancer (category C20) includes 1,244 individuals and 451,020 controls. In addition, we derived CRC gene expression datasets from the NCBI-GEO (GSE106582). The chemicals related gene sets were acquired from the comparative toxicogenomics database (CTD). Transcriptome-wide association study (TWAS) analysis was applied to CRC GWAS summary data and calculated the expression association testing statistics by FUSION software. We performed chemicals related gene set enrichment analysis (GSEA) by integrating GWAS summary data, mRNA expression profiles of CRC and the CTD chemical-gene interaction networks to identify relationships between chemicals and genes of CRC. We observed several significant correlations between chemicals and CRC. Meanwhile, we also detected 5 common chemicals between colon and rectal cancer, including methylnitronitrosoguanidine, isoniazid, PD 0325901, sulindac sulfide, and importazole. Our study performed TWAS and GSEA analysis, linked prior knowledge to newly generated data and thereby helped identifying chemicals related to tumor genes, which provides new clues for revealing the associations between environmental chemicals and cancer.
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- 2020
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50. Identification of Protein Expression Changes in Hepatocellular Carcinoma through iTRAQ
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Suxia Han, Xia Ying, Dan Zhang, Jinlu Ma, Yuanyuan Zhang, Chenchen He, and Qian Zhao
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Male ,Proteomics ,0301 basic medicine ,Medicine (General) ,Clinical Biochemistry ,0302 clinical medicine ,biology ,Liver Neoplasms ,General Medicine ,Middle Aged ,PON1 ,Gene Expression Regulation, Neoplastic ,C-Reactive Protein ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,Biomarker (medicine) ,Female ,Research Article ,Adult ,Carcinoma, Hepatocellular ,Article Subject ,Down-Regulation ,Peroxiredoxin 2 ,Malignancy ,03 medical and health sciences ,Text mining ,R5-920 ,Downregulation and upregulation ,Biomarkers, Tumor ,Genetics ,medicine ,Humans ,Molecular Biology ,neoplasms ,Aged ,Aryldialkylphosphatase ,business.industry ,Gene Expression Profiling ,Biochemistry (medical) ,Paraoxonase ,Peroxiredoxins ,medicine.disease ,Survival Analysis ,digestive system diseases ,030104 developmental biology ,Case-Control Studies ,alpha 1-Antitrypsin ,Cancer research ,biology.protein ,business - Abstract
Background. Hepatocellular carcinoma (HCC) is a malignant tumor associated with a poor prognosis. Serum biomarkers of HCC have the potential to improve the diagnosis, provide a means to monitor the tumors, and predict their malignancy. Proteins that are expressed differentially between HCC patients and normal controls have the potential to be biomarkers. Method. Serum samples from 10 confirmed HCC patients and 10 controls were collected. The differentially expressed proteins in the serum were identified using an isobaric tags for relative and absolute quantitation- (iTRAQ-) based method. Potential serum biomarkers were validated by ELISA in another 20 HCC patients and 20 controls. Their expression data in HCC were extracted from The Cancer Genome Atlas (TCGA) dataset. Results. A total of 260 proteins were measured in the serum of HCC patients and compared to those in sex- and age-matched normal controls. Forty-one proteins displayed significant changes, with 26 being downregulated and 15 being upregulated. Upregulated proteins included alpha-1-antitrypsin (A1AT) and peroxiredoxin 2 (PRDX2), and downregulated proteins included paraoxonase 1 (PON1) and C-reactive protein (CRP). We then used ELISA to measure serum levels of A1AT, PRDX2, PON1, and CRP in another 20 patients with HCC and found that only PON1 levels were consistent with the iTRAQ result. In TCGA dataset, PON1 expression was downregulated in HCC tissues (P<0.001) and low expression of PON1 was associated with poor survival in HCC patients (P<0.001). Conclusions. PON1 could act as a biomarker for HCC to assist in the diagnosis of HCC.
- Published
- 2020
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