25 results on '"Fu, Ziyi"'
Search Results
2. Comprehensive description of the current breast cancer microenvironment advancements via single-cell analysis
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Yan, Xueqi, Xie, Yinghong, Yang, Fan, Hua, Yijia, Zeng, Tianyu, Sun, Chunxiao, Yang, Mengzhu, Huang, Xiang, Wu, Hao, Fu, Ziyi, Li, Wei, Jiao, Shiping, and Yin, Yongmei
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- 2021
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3. An Imbalance in Histone Modifiers Induces tRNA-Cys-GCA Overexpression and tRF-27 Accumulation by Attenuating Promoter H3K27me3 in Primary Trastuzumab-Resistant Breast Cancer.
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Duan, Ningjun, Hua, Yijia, Yan, Xueqi, He, Yaozhou, Zeng, Tianyu, Gong, Jue, Fu, Ziyi, Li, Wei, and Yin, Yongmei
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RNA physiology ,PROTEINS ,DRUG resistance in cancer cells ,TRASTUZUMAB ,RESEARCH funding ,BREAST tumors ,CELL physiology ,TRANSCRIPTION factors ,HISTONES ,GENE expression ,MOLECULAR structure - Abstract
Simple Summary: tRF-27 has been identified as upregulated in both naïve trastuzumab-resistant HER2-positive breast cancer cells and patient samples, positioning it as a potential biomarker. However, the underlying mechanisms of this upregulation remain unclear. This study proposes that the abnormal transcription of specific tRNA-Cys-GCA isodecoders in naïve trastuzumab-resistant cells might contribute to the accumulation of tRF-27. Additionally, the reduction in H3K27me3 modifications at these tRNA genes, attributed to imbalances in histone modification enzymes, appears to influence tRNA transcription alterations. Building upon these findings, our research demonstrates that the application of a demethylase inhibitor may offer a potential strategy to overcome trastuzumab resistance. tRNA-derived fragments (tRFs) play crucial roles in cancer progression. Among them, tRF-27 has been identified as a key factor in promoting naïve trastuzumab resistance in HER2-positive breast cancer. However, the origin of tRF-27 remains uncertain. In this study, we propose that the upregulated expression of specific cysteine tRNAs may lead to the increased accumulation of tRF-27 in trastuzumab-resistant JIMT1 cells. Mechanistically, the reduced inhibitory H3K27me3 modification at the promoter regions of tRF-27-related tRNA genes in JIMT1 cells, potentially resulting from decreased EZH2 and increased KDM6A activity, may be a critical factor stimulating the transcriptional activity of these tRNA genes. Our research offers fresh insights into the mechanisms underlying elevated tRF-27 levels in trastuzumab-resistant breast cancer cells and suggests potential strategies to mitigate trastuzumab resistance in clinical treatments. [ABSTRACT FROM AUTHOR]
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- 2024
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4. Lapatinib in combination with capecitabine versus continued use of trastuzumab in breast cancer patients with trastuzumab-resistance: a retrospective study of a Chinese population
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Yang, Fan, Huang, Xiang, Sun, Chunxiao, Li, Jianbin, Wang, Biyun, Yan, Min, Jin, Feng, Wang, Haibo, Zhang, Jin, Fu, Peifen, Zeng, Tianyu, Wang, Jian, Li, Wei, Li, Yongfei, Yang, Mengzhu, Li, Jun, Wu, Hao, Fu, Ziyi, Yin, Yongmei, and Jiang, Zefei
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- 2020
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5. Exosome-Transmitted tRF-16-K8J7K1B Promotes Tamoxifen Resistance by Reducing Drug-Induced Cell Apoptosis in Breast Cancer.
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Sun, Chunxiao, Huang, Xiang, Li, Jun, Fu, Ziyi, Hua, Yijia, Zeng, Tianyu, He, Yaozhou, Duan, Ningjun, Yang, Fan, Liang, Yan, Wu, Hao, Li, Wei, Zhang, Yuchen, and Yin, Yongmei
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NUCLEOTIDE metabolism ,EXOSOMES ,TRANSFER RNA ,APOPTOSIS ,GENE expression ,TUMOR necrosis factors ,RESEARCH funding ,TAMOXIFEN ,PROGRESSION-free survival ,EXTRACELLULAR space ,CELL lines ,DRUG resistance in cancer cells ,BREAST tumors ,CASPASES ,PHARMACODYNAMICS - Abstract
Simple Summary: While the prognosis of hormone receptor-positive (HR+) breast cancer has been significantly improved, tamoxifen resistance remains a challenge in the treatment of HR+ breast cancer. This study identified that tRF-16-K8J7K1B, a novel small ncRNA derived from the 3′-end of tRNA
Ala-TGC , was highly expressed in tamoxifen-resistant cells compared to parental cells. Moreover, extracellular tRF-16-K8J7K1B confers tamoxifen resistance via incorporation into exosomes and then degrades the expression of apoptosis-related proteins, reducing the proportion of drug-induced cell apoptosis. Therefore, we propose that exosomal tRF-16-K8J7K1B could be a potential predictive biomarker and therapeutic target for overcoming tamoxifen resistance. Tamoxifen resistance remains a challenge in hormone receptor-positive (HR+) breast cancer. Recent evidence suggests that transfer ribonucleic acid (tRNA)-derived fragments play pivotal roles in the occurrence and development of various tumors. However, the relationship between tRNA-derived fragments and tamoxifen resistance remains unclear. In this study, we found that the expression of tRF-16-K8J7K1B was upregulated in tamoxifen-resistant cells in comparison with tamoxifen-sensitive cells. Higher levels of tRF-16-K8J7K1B were associated with shorter disease-free survival in HR+ breast cancer. Overexpression of tRF-16-K8J7K1B promotes tamoxifen resistance. Moreover, extracellular tRF-16-K8J7K1B could be packaged into exosomes and could disseminate tamoxifen resistance to recipient cells. Mechanistically, exosomal tRF-16-K8J7K1B downregulates the expression of apoptosis-related proteins, such as caspase 3 and poly (ADP-ribose) polymerase, by targeting tumor necrosis factor-related apoptosis-inducing ligand in receptor cells, thereby reducing drug-induced cell apoptosis. Therapeutically, the inhibition of exosomal tRF-16-K8J7K1B increases the sensitivity of breast cancer cells to tamoxifen in vivo. These data demonstrate that exosomal tRF-16-K8J7K1B may be a novel therapeutic target to overcome tamoxifen resistance in HR+ breast cancer. [ABSTRACT FROM AUTHOR]- Published
- 2023
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6. Nonmetastatic breast cancer patients subsequently developing second primary malignancy: A population‐based study.
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Bao, Shengnan, Jiang, Mengping, Wang, Xi, Hua, Yijia, Zeng, Tianyu, Yang, Yiqi, Yang, Fan, Yan, Xueqi, Sun, Chunxiao, Yang, Mengzhu, Fu, Ziyi, Huang, Xiang, Li, Jun, Wu, Hao, Li, Wei, Tang, Jinhai, and Yin, Yongmei
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BREAST cancer ,SECONDARY primary cancer ,CANCER patients ,PROGNOSIS ,MEDICAL personnel - Abstract
Background: With life span extending, breast cancer (BC) survivors may face the possibility of developing second primary cancer (SPC) and considerably shorten survivorship. However, little is known about multiple primary cancer (MPC) patients with nonmetastatic breast cancer as a first primary malignancy (BCFPM). Methods: Here, we retrospectively analyzed data on cancer survivors with BCFPM diagnosed between 2010 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database. The prognostic factors for breast cancer‐specific survival (BCSS) were ascertained by the stepwise regression analysis and a competing risk model, and were integrated to the establishment of prognostic nomogram, of which the accuracy was measured by the calibration curve and the concordance index (C‐index). Results: In total, 8616 patients were identified with 4.6% of 3‐year breast cancer‐ specific death (BCSD) and 8.6% of 5‐year BCSD. The most common SPC among BCFPM patients were female BC and lung cancer. Besides, the median latency time between BC and SPC was 22 months. At a ratio of 7:3, all patients were randomly categorized into a training cohort (n = 6032) and a validation cohort (n = 2584). By a proportional subdistribution hazards regression analysis, the following factors were considered to own independent prognostic abilities of BCSS: subtypes, grade, T classification, N classification, radiation, and sites of SPC. The nomogram could accurately predict 3‐year and 5‐year breast cancer‐associated survival of BCFPM patients with high internal and external validated C‐index, 0.715 (95% CI, 0.691–0.739), and 0.683 (95% CI, 0.642–0.724), respectively. Conclusions: BC survivors remained a high risk of developing SPC and considerably shortened survival time. In this study, a favorable nomogram was constructed to as a prediction model for 3‐year and 5‐year BCSS of BCFPM patients, largely intending to prolong the life of these patients by assisting clinicians to make individualized follow‐up plans. [ABSTRACT FROM AUTHOR]
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- 2021
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7. Risk Signature of Cancer-Associated Fibroblast–Secreted Cytokines Associates With Clinical Outcomes of Breast Cancer.
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Sun, Chunxiao, Wang, Siwei, Zhang, Yuchen, Yang, Fan, Zeng, Tianyu, Meng, Fanchen, Yang, Mengzhu, Yang, Yiqi, Hua, Yijia, Fu, Ziyi, Li, Jun, Huang, Xiang, Wu, Hao, Yin, Yongmei, and Li, Wei
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TREATMENT effectiveness ,CANCER prognosis ,OVERALL survival ,BREAST cancer ,CYTOKINES ,MAST cell disease ,MENARCHE - Abstract
Cancer-associated fibroblasts (CAFs) are key components in tumor microenvironment (TME). The secreted products of CAFs play important roles in regulating tumor cells and further impacting clinical prognosis. This study aims to reveal the relationship between CAF-secreted cytokines and breast cancer (BC) by constructing the risk signature. We performed three algorithms to reveal CAF-related cytokines in the TCGA BC dataset and identified five prognosis-related cytokines. Then we used single-cell RNA sequencing (ScRNA-Seq) datasets of BC to confirm the expression level of these five cytokines in CAFs. METABRIC and other independent datasets were utilized to validate the findings in further analyses. Based on the identified five-cytokine signature derived from CAFs, BC patients with high-risk score (RS) had shorter overall survival than low-RS cases. Further analysis suggested that the high-RS level correlated with cell proliferation and mast cell infiltration in BCs of the Basal-like subtype. The results also indicated that the level of RS could discriminate the high-risk BC cases harboring driver mutations (i.e., PI3KCA, CDH1, and TP53). Additionally, the status of five-cytokine signature was associated with the frequency and molecular timing of whole genome duplication (WGD) events. Intratumor heterogeneity (ITH) analysis among BC samples indicated that the high-RS level was associated with the increase of tumor subclones. This work demonstrated that the prognostic signature based on CAF-secreted cytokines was associated with clinical outcome, tumor progression, and genetic alteration. Our findings may provide insights to develop novel strategies for early intervention and prognostic prediction of BC. [ABSTRACT FROM AUTHOR]
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- 2021
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8. Comprehensive Analysis of lncRNA and miRNA Regulatory Network Reveals Potential Prognostic Non-coding RNA Involved in Breast Cancer Progression.
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Gao, Sheng, Lu, Xun, Ma, Jingjing, Zhou, Qian, Tang, RanRan, Fu, Ziyi, Wang, Fengliang, Lv, Mingming, and Lu, Cheng
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NON-coding RNA ,LINCRNA ,BREAST cancer ,CANCER invasiveness ,MICRORNA ,OVERALL survival - Abstract
Breast cancer is one of the most common malignant tumors in women and is the second leading cause of cancer deaths among women. The tumorigenesis and progression of breast cancer are not well understood. The existing researches have indicated that non-coding RNAs, which mainly include long non-coding RNA (lncRNA) and microRNA (miRNA), have gradually become important regulators of breast cancer. We aimed to screen the differential expression of miRNA and lncRNA in the different breast cancer stages and identify the key non-coding RNA using TCGA data. Based on series test of cluster (STC) analysis, bioinformatics analysis, and negatively correlated relationships, 122 lncRNAs, 67 miRNAs, and 119 mRNAs were selected to construct the regulatory network of lncRNA and miRNA. It was shown that the miR-93/20b/106a/106b family was at the center of the regulatory network. Furthermore, 6 miRNAs, 10 lncRNAs, and 15 mRNAs were significantly associated with the overall survival (OS, log-rank P < 0.05) of patients with breast cancer. Overexpressed miR-93 in MCF-7 breast cancer cells was associated with suppressed expression of multiple lncRNAs, and these downregulated lncRNAs (MESTIT1, LOC100128164, and DNMBP-AS1) were significantly associated with poor overall survival in breast cancer patients. Therefore, the miR-93/20b/106a/106b family at the core of the regulatory network discovered by our analysis above may be extremely important for the regulation of lncRNA expression and the progression of breast cancer. The identified key miRNA and lncRNA will enhance the understanding of molecular mechanisms of breast cancer progression. Targeting these key non-coding RNA may provide new therapeutic strategies for breast cancer treatment and may prevent the progression of breast cancer from an early stage to an advanced stage. [ABSTRACT FROM AUTHOR]
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- 2021
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9. Serum tRNA‐derived fragments (tRFs) as potential candidates for diagnosis of nontriple negative breast cancer.
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Huang, Yue, Ge, Han, Zheng, Mingjie, Cui, Yangyang, Fu, Ziyi, Wu, Xiaowei, Xia, Yiqin, Chen, Lie, Wang, Zhenghui, Wang, Shui, and Xie, Hui
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BREAST cancer ,POLYMERASE chain reaction ,NEEDLE biopsy ,BREAST imaging - Abstract
Breast cancer has become the most common cancer in women, and nontriple negative breast cancer (non‐TNBC) accounts for 80–90% of all invasive breast cancers. Early detection, diagnosis, and treatment are considered key to a successful cure. Conventionally, breast imaging and needle core biopsy are used for detection and monitoring. However, small variations in volume might be ignored in imaging, and traditional biopsies are spatially and temporally limited, leading to a significant delay in cancer detection and thus prompting renewed focus on early and accurate diagnosis. In this article, we investigated whether there is an accurate molecule in peripheral blood that can help diagnose breast cancer. Similar to microRNAs, tRNA‐derived fragments (tRFs) have been reported to be involved in many pathological processes in breast cancer, but whether they can serve as candidate biomarkers for breast cancer remains unclear. Using high‐throughput sequencing technology, we identified 4,021 differentially expressed tRFs in normal and breast cancer cell lines, and eight tRFs were selected to establish a signature as a predictive biomarker of non‐TNBC. Furthermore, quantitative reverse‐transcriptase polymerase chain reaction was performed to verify the expression of the signature and analyze the correlation between dysregulated tRFs and breast cancer. The results indicated that tDR‐7816, tDR‐5334, and tDR‐4733 might be promising biomarkers. Through further bioinformatics analysis, we predicted that tDR‐7816 influences the xenobiotic metabolic processes that support the oncogenesis of breast cancer. In summary, our results provide a rationale for using circulating tDR‐7816 expression as a novel potential biomarker for the diagnosis of patients with early non‐TNBC. [ABSTRACT FROM AUTHOR]
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- 2020
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10. Expression pattern of microRNAs related with response to trastuzumab in breast cancer.
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Yang, Fan, Fu, Ziyi, Yang, Mengzhu, Sun, Chunxiao, Li, Yongfei, Chu, Jiahui, Zhang, Yanhong, Li, Wei, Huang, Xiang, Li, Jun, Wu, Hao, Ding, Xiaorong, and Yin, Yongmei
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BREAST cancer , *RECEIVER operating characteristic curves , *POLYMERASE chain reaction , *PROTEIN-protein interactions , *BREAST cancer patients - Abstract
Background: Although an immense effort has been made to develop a novel biomarker for response to trastuzumab, no reliable biomarkers are available to guide management, expect for HER2. The aim of this study was to examine the relationship between microRNA (miRNA) expression and resistance to trastuzumab. Methods: Differentially expressed miRNAs between trastuzumab‐resistant and trastuzumab‐sensitive cell lines were analyzed using microarrays. We performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses to determine the functions of differentially expressed miRNA and their targeted genes. Furthermore, the protein–protein interactions (PPI) network was analyzed. Serum samples were collected from patients with HER2‐positive breast cancer who were treated with trastuzumab. We validated the miRNAs expression levels by quantitative reverse‐transcription polymerase chain reaction (qRT‐PCR) in these serums. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the predictive performance of the miRNA. Results: Using miRNA microarrays, 151 miRNAs that significant differentially expressed between the trastuzumab‐resistant and sensitive cells were identified, including 46 upregulated and 105 downregulated miRNAs. Results of real‐time PCR confirmed seven miRNAs in cell lines. PI3K‐Akt signaling pathway was involved in regulating biological function according to KEGG analysis. Compared with the serums of trastuzumab‐sensitive patients, three miRNAs, namely miR‐200b, miR‐135b, and miR‐29a, were identified to be upregulated, and miR‐224 was downregulated in the trastuzumab‐resistant serums. ROC analysis showed that four miRNAs were correlated with trastuzumab resistance. Furthermore, three subnetwork modules of PPI network were obtained. Conclusion: The results indicated that miRNAs were reliable predictive biomarkers for response to trastuzumab. [ABSTRACT FROM AUTHOR]
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- 2019
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11. tRNA-Derived Fragments as Novel Predictive Biomarkers for Trastuzumab-Resistant Breast Cancer.
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Sun, Chunxiao, Yang, Fan, Zhang, Yanhong, Chu, Jiahui, Wang, Jian, Wang, Yifan, Zhang, Yanqiu, Li, Jun, Li, Yongfei, Fan, Ruihua, Li, Wei, Huang, Xiang, Wu, Hao, Fu, Ziyi, Jiang, Zefei, and Yin, Yongmei
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MICRORNA ,BREAST cancer ,BIOMARKERS ,TRASTUZUMAB ,CANCER treatment - Abstract
Background/Aims: Resistance to trastuzumab remains a common challenge to HER-2 positive breast cancer. Up until now, the underlying mechanism of trastuzumab resistance is still unclear. tRNA-derived small non-coding RNAs, a new class of small non-coding RNA (sncRNAs), have been observed to play an important role in cancer progression. However, the relationship between tRNA-derived fragments and trastuzumab resistance is still unknown.Methods: We detected the levels of tRNA-derived fragments expression in normal breast epithelial cell lines, trastuzumab-sensitive and -resistant breast cancer cell lines using high-throughput sequencing. qRT-PCR was conducted to validate the differentially expressed fragments in serums from trastuzumab-sensitive and -resistant patients. A receiver operating characteristic (ROC) curve analysis was performed to evaluate the power of specific tRNA-derived fragments. Progression-free survival (PFS) was analyzed using Cox-regression.Results: Our sequence results showed that tRNA-derived fragments were differentially expressed in the HBL-100, SKBR3, and JIMT-1 cell lines. tRF-30-JZOYJE22RR33 and tRF-27-ZDXPHO53KSN were found significantly upregulated in trastuzumab-resistant patients compared to sensitive individuals, and the ROC analysis showed that tRF-30-JZOYJE22RR33 and tRF-27-ZDXPHO53KSN were correlated with trastuzumab resistance. In a multivariate analysis, higher levels of tRF-30-JZOYJE22RR33 and tRF-27-ZDXPHO53KSN expression were associated with significantly shorter PFS in patients with metastatic HER-2 positive breast cancer.Conclusion: Our results suggest that tRF-30-JZOYJE22RR33 and tRF-27-ZDXPHO53KSN play important roles in trastuzumab resistance. Patients with high levels of tRF-30-JZOYJE22RR33 and tRF-27-ZDXPHO53KSN expression benefitted less from trastuzumab-based therapy than those that express lower-levels of these molecules. tRF-30-JZOYJE22RR33 and tRF-27-ZDXPHO53KSN may be potential biomarkers and intervention targets in the clinical treatment of trastuzumab-resistant breast cancer. [ABSTRACT FROM AUTHOR]- Published
- 2018
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12. Cancer/testis antigen‐Plac1 promotes invasion and metastasis of breast cancer through Furin/NICD/PTEN signaling pathway.
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Li, Yongfei, Chu, Jiahui, Li, Jun, Feng, Wanting, Yang, Fan, Wang, Yifan, Zhang, Yanhong, Sun, Chunxiao, Yang, Mengzhu, Vasilatos, Shauna N., Huang, Yi, Fu, Ziyi, and Yin, Yongmei
- Abstract
Placenta‐specific protein 1 (Plac1) is a cancer/testis antigen that plays a critical role in promoting cancer initiation and progression. However, the clinical significance and mechanism of Plac1 in cancer progression remain elusive. Here, we report that Plac1 is an important oncogenic and prognostic factor, which physically interacts with Furin to drive breast cancer invasion and metastasis. We have shown that Plac1 expression positively correlates with clinical stage, lymph node metastasis, hormone receptor status, and overall patient survival. Overexpression of Plac1 promoted invasion and metastasis of breast cancer cells in vitro and in vivo. Co‐immunoprecipitation and immunofluorescence cell staining assays revealed that interaction of Plac1 and Furin degraded Notch1 and generated Notch1 intracellular domain (NICD) that could inhibit PTEN activity. These findings are consistent with the results of microarray study in MDA‐MB‐231 cells overexpressing Plac1. A rescue study showed that inhibition of Furin and overexpression of PTEN in Plac1 overexpression cells blocked Plac1‐induced tumor cell progression. Taken together, our findings suggest that functional interaction between Plac1 and Furin enhances breast cancer invasion and metastasis and the Furin/NICD/PTEN axis may act as an important therapeutic target for breast cancer treatment. [ABSTRACT FROM AUTHOR]
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- 2018
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13. Chemoresistance-related long non-coding RNA expression profiles in human breast cancer cells.
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Huang, Lei, Zeng, Lihua, Chu, Jiahui, Xu, Pengfei, Lv, Mingming, Xu, Juan, Wen, Juan, Li, Wenqu, Wang, Luyu, Wu, Xiaowei, Fu, Ziyi, Xie, Hui, and Wang, Shui
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NON-coding RNA ,BREAST cancer ,CANCER chemotherapy ,MICROARRAY technology ,DOXORUBICIN - Abstract
Breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death in females worldwide. Chemoresistance has been a major reason for the drug therapy failure. The present study performed a microarray analysis between MCF-7 and MCF-7/adriamycin (ADR) cells, and intended to identify long non-coding (lnc)RNA expression character in drug resistant breast cancer cells. MCF-7/ADR cells were induced from MCF-7 cells via pulse-selection with doxorubicin for 4 weeks, and the resistance to doxorubicin of ADR cells was confirmed by MTT assay. Microarray analysis was performed between MCF-7 and MCF-7/ADR cells. Total RNA was extracted from the two cell lines respectively and was transcribed into cDNA. The results of the microarray were verified by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Gene Ontology (GO) and pathways analysis were conducted to enrich the dysregulated lncRNAs presented in the microarray results. Compared to the MCF-7 cells, 8,892 lncRNAs were differentially expressed in MCF/ADR cells (absolute fold-change >2.0). A total of 32 lncRNAs were selected for RT-qPCR by fold-change filtering, standard Student's t-test, and multiple hypothesis testing. Among the dysregulated lncRNAs, AX747207 was prominent because its associated gene RUNX3 was previously reported to be relative to malignant tumor chemoresistance. GO analysis results also indicated some biological processes and molecular functions linked to chemoresistance. The pathway enrichment results provided some potential pathways associated with chemoresistance. In the present study, the authors intended to identify lncRNA expression character in drug resistant cell line MCF-7/ADR, corresponding to the parental MCF-7 cell line. In addition, the study identified the lncRNA AX747207, and its potential targeted gene RUNX3, may be related to chemoresistance in breast cancer. These results may new insights into exploring the mechanisms of chemoresistance in breast cancer. [ABSTRACT FROM AUTHOR]
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- 2018
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14. MicroRNA-132 and microRNA-212 mediate doxorubicin resistance by down-regulating the PTEN-AKT/NF-κB signaling pathway in breast cancer.
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Xie, Manxin, Fu, Ziyi, Cao, Jianxiang, Liu, Yuan, Wu, Jie, Li, Qing, and Chen, Yun
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BREAST cancer treatment , *MULTIDRUG resistance , *MICRORNA , *LUCIFERASES , *DOXORUBICIN - Abstract
Breast cancer is a serious health problem worldwide. Acquisition of multi-drug resistance (MDR) during the treatment of breast cancer is still considered a major clinical obstacle. Despite the biological functions of miRNAs becoming increasingly apparent, the function of miRNAs in regulating drug resistance of breast cancer remains under investigation. Quantitative real-time PCR (qRT-PCR) was used to quantify the expression of miR-132/-212 (miR-132 and miR-212) in doxorubicin (DOX)-resistant and -sensitive breast cancer tumors and cells. The function of miR-132/-212 in drug resistance was investigated in vitro (MTT assay, TUNEL assay, fluorescence, immunohistochemistry, luciferase reporter assay, Western blotting). We found that miR-132/-212 were commonly overexpressed in DOX-resistant breast cancer tumors and cells. Silenced miR-132/-212 expression induced DOX accumulation in MCF-7/ADR cells, while overexpression of miR-132/-212 led to breast cancer resistance protein (BCRP)-based DOX efflux in MCF-7 cells. Further study showed that up-regulation of miR-132/-212 in MCF-7/ADR cells suppressed the expression of PTEN, a target gene of miR-132/-212, which activated AKT phosphorylation and the NF-κB pathway and led to increased BCRP expression. Down-regulation of miR-132/-212 sensitized MCF-7/ADR cells to DOX. Mechanistic investigations suggested that miR-132/-212 enhancement was a result of NF-κB-mediated transactivation of the pri-miR-132/-212 gene. Taken together, our findings are among the first to demonstrate a novel aspect of the miR-132/-212-PTEN-AKT/NF-κB-BCRP pathway in the generation of breast cancer resistance and provides a potential method to reverse drug resistance. [ABSTRACT FROM AUTHOR]
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- 2018
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15. Promotion of breast cancer cells MDA-MB-231 invasion by di(2-ethylhexyl)phthalate through matrix metalloproteinase-2/-9 overexpression.
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Zhang, Shuya, Ma, Jiehua, Fu, Ziyi, Zhang, Zhilei, Cao, Jian, Huang, Lei, Li, Wenqu, Xu, Pengfei, and Cao, Xin
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PHTHALATE esters ,MATRIX metalloproteinases ,GENETIC overexpression ,CANCER cells ,POLYMERASE chain reaction ,WESTERN immunoblotting ,IMMUNOFLUORESCENCE - Abstract
Di(2-ethylhexyl)phthalate (DEHP) is an estrogenic chemical that is widely used in polyvinyl products. We aimed to determine the mechanisms behind the effects of DEHP on ERα-negative breast cancer cells MDA-MB-231 invasion and matrix metalloproteinases-2/-9 (MMP-2/-9) up-regulation in this study. Transwell assay indicated that DEHP exposure (>50 μg/ml) significantly enhanced the invasion ability of MDA-MB-231 cells. Quantitative real-time PCR (qPCR) and western blotting revealed that MMP-2/-9 is overexpressed in mRNA and protein levels after DEHP treatment. Gelatin zymography consistently demonstrated that DEHP exposure also enhances the activity of MMP-2/-9. Immunofluorescence assay showed that DEHP could accelerate NF-kappaB (NF-κB) subunits-p65 translocation into the nucleus, which is confirmed by western blotting assay, suggesting that the ratio of nuclear/cytosolic level of p65 was significantly increased. Furthermore, the invasion and MMP-2/-9 overexpression of MDA-MB-231 cells after DEHP-treated were reversed by the NF-κB chemical inhibitor JSH-23 via drug inhibition assay. This study suggested that DEHP could promote ERα-negative breast cancer cells MDA-MB-231 invasion through activating NF-κB and MMP-2/-9 overexpression. [ABSTRACT FROM AUTHOR]
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- 2016
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16. Comprehensive profiling of biological processes reveals two major prognostic subtypes in breast cancer.
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Chen, Fei, Gao, Sheng, Wang, Fengliang, Ma, Jingjing, Zhang, Min, Lv, Mingming, Zhou, Qian, Fu, Ziyi, Lu, Cheng, and Yin, Hong
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Heterogeneity is the major obstacle to breast cancer target therapy. Classification of breast cancer with significant biological process may reduce the influence of heterogeneity of intrinsic tumor. We used survival analysis to filter 95 gene sets and classify 638 breast cancer samples into two subtypes based on those gene sets associated with prognosis. Clinical outcome of two subtypes were evaluated with disease-free survival, distant metastasis-free survival, and overall survival levels in three databases and ER+, PR+ HER2+, and TNBC groups. We established a novel classification with 95 prognostic gene sets. In the training and validation cohorts, the subtype 1 was characterized by significant gene sets associated with regulation of metabolic process and enzyme activity and predicted obviously improved clinical outcome than subtype 2, which was enriched by tumor cell division, mitosis, and cell cycle-related gene sets ( P < 0.05). When evaluated prognostic impact of subtypes in ER+, PR+ HER2+, and TNBC groups, we found that patients in subtype 1 showed better prognosis in ER+ and PR+ groups ( P < 0.05) but had no difference from prognosis of subtype 2 in HER2+ and TNBC groups. These findings may have implications in understanding of breast cancer and filtering effective therapeutic strategies for targeted therapy. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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17. Systematic analysis of gene expression pattern in has-miR-760 overexpressed resistance of the MCF-7 human breast cancer cell to doxorubicin.
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Lv, Jianxin, Fu, Ziyi, Shi, Min, Xia, Kai, Ji, Chenbo, Xu, Pengfei, Lv, Mingming, Pan, Bo, Dai, Luxian, and Xie, Hui
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BREAST cancer treatment , *DOXORUBICIN , *MICRORNA genetics , *DRUG resistance in cancer cells , *G proteins , *GENE expression , *REVERSE transcriptase polymerase chain reaction - Abstract
Background/Aims Chemoresistance of breast cancer is a growing problem and still a major clinical obstacle to successful treatment in clinical patients. miR-760 was significantly downregulated in chemoresistance breast cancer tissues compared to chemo-sensitive tissues in our previous study. However, the role of miR-760 in modulating drug resistance remains largely unexplored. In this study, we sought to determine the expression pattern of miR-760 targeted mRNAs, and explore their potential functions and participated-pathways in breast cancer drug resistance cells. Results Compared to parental cell line MCF-7, miR-760 was downregulated by 6.15 folds in MCF-7/Adr cells. The qRT-PCR result showed that compared to miR-760 negative control cells group, miR-760 was up-regulated 15.817 folds after miR-760 lentiviral transfection in miR-760 mimics group. The microarray data showed that 270 genes were dysregulated over 2-fold change in MCF-7/Adr cells after miR-760 overexpressed, including 241 up-regulated and 29 downregulated genes. GO analysis result appeared that the predicted target genes of miR-760 mainly regulated DNA binding, protein binding, molecular function, nucleic acid binding, and so on; the pathway analysis data demonstrated that these target genes mainly involved in cell cycle, TGF-beta signaling pathway, mRNA processing reactome, G protein signaling, apoptosis, Wnt signaling pathway, and other signaling pathways. There were 3 predicted target genes ( RHOB , ANGOTL4 , ABCA1 ) of miR-760 were selected at a P value < 0.05 and the fold enrichment was > 40. Conclusion Our study explored the genes expression pattern after miR-760 overexpresssed, and confirmed 3 dominantly dysregulated genes, which could expand the insights into the miR-760 function and molecular mechanisms in drug resistance of breast cancer. This study might afford a comprehensive understanding of miR-760 as prognostic biomarkers during clinical treatment, and we supposed that the miR-760 expression levels in drug resistance carcinoma tissues could be pursued to develop new strategies for targeted therapies in chemoresistant breast cancer patients. [ABSTRACT FROM AUTHOR]
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- 2015
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18. Mammary Fat of Breast Cancer: Gene Expression Profiling and Functional Characterization.
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Wang, Fengliang, Gao, Sheng, Chen, Fei, Fu, Ziyi, Yin, Hong, Lu, Xun, Yu, Jing, and Lu, Cheng
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ADIPOSE tissues ,BREAST cancer ,GENE expression ,HORMONES ,GROWTH factors ,STROMAL cells - Abstract
Mammary fat is the main composition of breast, and is the most probable candidate to affect tumor behavior because the fat produces hormones, growth factors and adipokines, a heterogeneous group of signaling molecules. Gene expression profiling and functional characterization of mammary fat in Chinese women has not been reported. Thus, we collected the mammary fat tissues adjacent to breast tumors from 60 subjects, among which 30 subjects had breast cancer and 30 had benign lesions. We isolated and cultured the stromal vascular cell fraction from mammary fat. The expression of genes related to adipose function (including adipogenesis and secretion) was detected at both the tissue and the cellular level. We also studied mammary fat browning. The results indicated that fat tissue close to malignant and benign lesions exhibited distinctive gene expression profiles and functional characteristics. Although the mammary fat of breast tumors atrophied, it secreted tumor growth stimulatory factors. Browning of mammary fat was observed and browning activity of fat close to malignant breast tumors was greater than that close to benign lesions. Understanding the diversity between these two fat depots may possibly help us improve our understanding of breast cancer pathogenesis and find the key to unlock new anticancer therapies. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
19. Serum proteomics analysis of candidate predictive biomarker panel for the diagnosis of trastuzumab-based therapy resistant breast cancer.
- Author
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Yang, Ting, Fu, Ziyi, Zhang, Yin, Wang, Min, Mao, Changfei, and Ge, Weihong
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TRIPLE-negative breast cancer , *HORMONE receptor positive breast cancer , *BREAST cancer , *BLOOD serum analysis , *EPIDERMAL growth factor receptors , *BLOOD proteins - Abstract
• Aimed to identify serum biomarkers for predicting the efficacy of trastuzumab-based therapy to HER2-positive breast cancer. • TMT label-based quantitative proteomics discovered 18 differentially expressed proteins in the serum. • MRM approach-based targeted proteomics identified SRGN, LDHA and CST3 as candidate biomarkers. • Trastuzumab-based therapy resistance diagnostic score was established based on the level of SRGN, LDHA and CST3. Human epidermal growth factor receptor 2 (HER2)-positive is a particularly aggressive type of the breast cancer. Trastuzumab-based therapy is a standard treatment for HER2-positive breast cancer, but some patients are resistant to the therapy. Serum proteins have been used to predict therapeutic benefit for various cancers, but whether serum proteins can serve as biomarkers for HER2-positive breast cancer remains unclear. Using an isobaric Tandem Mass Tag (TMT) label-based quantitative proteomic, we discovered 18 differentially expressed proteins in the serum of trastuzumab-based therapy resistant patients before therapy. Then, four proteins were selected and validated using an LC–MS/MS-based multiple reaction monitoring quantification method, and it was confirmed that three proteins (SRGN, LDHA and CST3) were correlated with trastuzumab-based therapy resistance. Finally, the trastuzumab-based therapy resistance diagnostic score was calculated and acquired by means of a logistic regression pattern based on the level of these three proteins. In summary, we develop a serum-based protein signature that potentially predicts the therapeutic effects of trastuzumab-based therapy for HER2-positive breast cancer patients. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
20. Chemoresistance-related long non-coding RNA expression profiles in human breast cancer cells.
- Author
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Huang, Lei, Zeng, Lihua, Chu, Jiahui, Xu, Pengfei, Lv, Mingming, Xu, Juan, Wen, Juan, Li, Wenqu, Wang, Luyu, Wu, Xiaowei, Fu, Ziyi, Xie, Hui, and Wang, Shui
- Subjects
BREAST cancer ,RNA ,GENE expression - Abstract
A correction is presented to the article "Chemoresistance‑related long non‑coding RNA expression profiles in human breast cancer cells" which was published in a 2019 issue of the periodical.
- Published
- 2019
21. Differential DNA methylation status between breast carcinomatous and normal tissues.
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Wang, Fengliang, Yang, Yafang, Fu, Ziyi, Xu, Nan, Chen, Fei, Yin, Hong, Lu, Xun, Shen, Rong, and Lu, Cheng
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- *
BREAST cancer , *DNA methylation , *TISSUES , *MICROARRAY technology , *CHROMOSOMES , *POLYMERASE chain reaction - Abstract
Breast cancer has been considered to be a multifactorial disease with a wide array of well-characterized gene mutations and chromosomal abnormalities. However, it is becoming evident that the onset or development of breast cancer also depends on epigenetic factors, although the mechanisms have not been fully elucidated. We performed a genome-wide analysis of DNA methylation of breast carcinomatous tissues and paired normal tissues to examine the differences in methylation between them. Methylation-specific polymerase chain reaction (MSP) was used to validate the hypermethylated genes screened out by DNA methylation microarray. We found that hypomethylation and hypermethylation occurred in 2753 and 1795 genes, respectively, in breast carcinomatous tissues. Meanwhile, gene ontology analysis and ingenuity pathway analysis revealed the function and pathway of several genes whose methylation status was altered in breast carcinomatous tissues. In addition, we investigated the promoter methylation status of four genes in breast carcinomatous tissue and paired normal tissues ( n = 30) by MSP. Promoter hypermethylation of CRABP1 , HOXB13 , IFNGR2 , and PIK3C3 was found in 37% (11/30), 23% (7/30), 17% (5/30), and 2% (2/30) of the carcinomas, respectively. Mutation of these four important genes was critical to many types of cancer. Our results suggest that DNA methylation mechanisms may be involved in regulating the occurrence and development of breast cancer. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
22. CircIRAK3 sponges miR-3607 to facilitate breast cancer metastasis.
- Author
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Wu, Jie, Jiang, Zerun, Chen, Chen, Hu, Qingsong, Fu, Ziyi, Chen, Junjie, Wang, Zhangding, Wang, Qiang, Li, Aiping, Marks, Jeffrey R., Guo, Changying, Chen, Yun, Zhou, Jianwei, Yang, Liuqing, Lin, Chunru, and Wang, Shouyu
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CIRCULAR RNA , *BREAST cancer , *METASTASIS , *NEOPLASTIC cell transformation , *DISEASE progression - Abstract
As a class of endogenous noncoding RNAs, circular RNAs (circRNAs) have been recently identified to regulate tumourigenesis and progression in multiple malignancies. However, the expression profiles and function of circRNAs in breast cancer metastasis are largely unknown. Here, we determined that the expression of a novel circRNA, which we named circIRAK3, was increased in metastatic breast cancer (BC) cells and predictive of BC recurrence. Gain-of-function and loss-of-function studies in BC cells demonstrated that circIRAK3 promoted cell migration, invasion and metastasis in vitro and in vivo but did not affect cell proliferation, colony formation or cell cycle progression. Using circIRAK3 in vivo precipitation and luciferase reporter assays, we identified miR-3607 as a circIRAK3-associated miRNA. Furthermore, RNA sequencing and bioinformatics analysis showed that forkhead box C1 (FOXC1), the target of miR-3607, was downregulated in circIRAK3-silenced cells and mediated circIRAK3-induced BC cell migration. Intriguingly, FOXC1 could, in turn, bind to the IRAK3 promoter, triggering a positive-feedback loop that perpetuated the circIRAK3/miR-3607/FOXC1 signaling axis. Collectively, our findings indicated that circIRAK3 may exert regulatory roles in BC metastasis and may be a potential target for metastatic BC therapy. [ABSTRACT FROM AUTHOR]
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- 2018
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23. 1,25(OH)2D3 deficiency increases TM40D tumor growth in bone and accelerates tumor-induced bone destruction in a breast cancer bone metastasis model.
- Author
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Lu, Guangping, Li, Jun, Chu, Jiahui, Jin, Shidai, Fu, Ziyi, Miao, Dengshun, and Yin, Yongmei
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BONE metastasis , *TUMOR growth , *BREAST cancer , *VITAMIN D , *CELL proliferation - Abstract
Breast cancer is one of the most common malignancies and bone is the commonest site of distant metastases. Evidences indicate that adequate supply of vitamin D will decrease the morbidity and mortality of breast cancer. However, the main role of vitamin D deficiency in breast cancer bone metastases remains unclear. In this study, the relationship between vitamin D and breast cancer bone metastases were evaluated. Results showed that 1,25(OH) 2 D 3 can not only inhibit the proliferation, migration and invasion of breast cancer cell TM40D in vitro, but also attenuate the breast cancer cell TM40D-induced bone destruction in vivo, whose underlying mechanism was at least partially through decreasing the number of the osteoclasts. To our knowledge, this is the first to use 1-alpha-hydroxylase [1α(OH)ase] knockout mice which characterized vitamin D deficiency to establish the breast cancer bone metastases model. Based on this model, we also found that vitamin D deficiency will accelerate the osteolytic lesions, and 1,25(OH) 2 D 3 supplement will restrain osteolytic lesions. Therefore, these findings suggest that vitamin D has the potential capacity to be a therapeutic agent for the breast cancer bone metastases. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
24. Roles of cancer/testis antigens (CTAs) in breast cancer.
- Author
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Li, Yongfei, Li, Jun, Wang, Yifan, Zhang, Yanhong, Chu, Jiahui, Sun, Chunxiao, Fu, Ziyi, Huang, Yi, Zhang, Hansheng, Yuan, Hongyan, and Yin, Yongmei
- Subjects
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BREAST cancer diagnosis , *IMMUNOTHERAPY , *TUMOR markers , *ANTIGENS , *CANCER-related mortality , *BREAST tumor treatment , *ANIMALS , *BREAST tumors , *DRUG therapy , *PROGNOSIS , *TESTIS tumors , *TUMOR antigens - Abstract
Breast cancer is the most common cancer diagnosed and is the second leading cause of cancer death among women in the US. For breast cancer, early diagnosis and efficient therapy remains a significant clinical challenge. Therefore, it is necessary to identify novel tumor associated molecules to target for biomarker development and immunotherapy. In this regard, cancer testis antigens (CTAs) have emerged as a potential clinical biomarker targeting immunotherapy for various malignancies due to the nature of its characteristics. CTAs are a group of tumor associated antigens (TAAs) that display normal expression in immune-privileged organs, but display aberrant expression in several types of cancers, particularly in advanced cancers. Investigation of CTAs for the clinical management of breast malignancies indicates that these TAAs have potential roles as novel biomarkers, with increased specificity and sensitivity compared to those currently used in the clinic. Moreover, TAAs could be therapeutic targets for cancer immunotherapy. This review is an attempt to address the promising CTAs in breast cancer and their possible clinical implications as biomarkers and immunotherapeutic targets with particular focus on challenges and future interventions. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
25. Identification and characterization of microRNAs expressed in human breast cancer chemo-resistant MCF-7/Adr cells by Solexa deep-sequencing technology.
- Author
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Xu, Pengfei, Wang, Luyu, Huang, Lei, Li, Wenqu, Lv, Shanshan, Lv, Mingming, Ma, Jingjing, Zhou, Qian, Wu, Xiaowei, Fu, Ziyi, Lu, Cheng, and Yin, Hong
- Subjects
- *
BREAST cancer patients , *BREAST cancer treatment , *MICRORNA , *SEQUENCE alignment , *GENE expression , *POLYMERASE chain reaction , *DRUG resistance in cancer cells - Abstract
Background/Aim Breast cancer is the most common type of tumor in female and chemoresistance has been a major clinical obstacle to the treatment in clinical patients. miRNA was one of the factors demonstrated to play certain roles in chemoesistance in breast cancer. In this study, we exploited Solexa deep sequencing technology to identify differentially expressed miRNA from samples in vitro, trying to find novel relationship between miRNA and chemoresistance in breast cancer. Methods The human breast cancer MCF-7 cell line was pulse-selected with doxorubicin (10 pulses, once a week for 4 h, with 1 μM doxorubicin) to generate MCF-7/Adr cells. Total RNA was extracted from the treated and untreated MCF-7 cells and subsequently subjected to real time PCR. Two small RNA libraries of MCF7NON and MCF7ADR were established to record the Solexa sequencing results of the PCR products above. All the sequencing results were verified by Stem-loop real-time PCR. GO annotation and KEGG analysis program were exploited to enrich the differentially expressed miRNAs. Results The results showed that 214,822 and 378,597 reads were mapped in the MCF7ADR and MCF7NON libraries when aligned to hairpin structure respectively. Meanwhile, 1323 and 520 reads were mapped when aligned to mature sequences. In addition, 310 known mature miRNAs were coexpressed in both libraries. Comparing the MCF7ADR group to the MCF7NON group, 18 miRNAs were significantly differentially expressed. GO annotation and KEGG analysis showed that the target genes were enriched in regulation of transcription and development as well as Wnt signaling pathway, MAPK signaling pathway and TGF-ß signaling pathway. Conclusion The results proved that the Solexa deep sequencing was a powerful and reliable platform to analyze small RNAs. And further investigation should be conducted for the biological process and pathways that have been identified and more efforts should be made to research the mechanism of chemoresistance in breast cancer. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
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