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Rui Sun,* Jinhui Liu,* Sipei Nie,* Siyue Li, Jing Yang, Yi Jiang, Wenjun Cheng Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wenjun ChengDepartment of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, People’s Republic of ChinaEmail wenjunchengdoc@163.comIntroduction: This bioinformatic study confirmed a new miRNA-mRNA regulatory network and a prognostic signature in endometrial cancer (EC).Materials and Methods: We downloaded RNA-seq and miRNA-seq data of EC from the TCGA database, then used EdegR package to screen differentially expressed miRNAs and mRNAs (DE-miRNAs and DE-mRNAs). Then, we constructed a regulatory network of EC-associated miRNAs and hub genes by Cytoscape, and determined the expression of unexplored miRNAs in EC tissues and normal adjacent tissues by quantitative Real-Time PCR (qRT-PCR). A prognostic signature model and a predictive nomogram were constructed. Finally, we explored the association between the prognostic model and the immune cell infiltration.Results: A total of 11,531 DE-mRNAs and 236 DE-miRNAs, as well as 275 and 118 candidate DEGs for upregulated and downregulated DE-miRNAs were screened out. The miRNA-mRNA network included 5 downregulated and 13 upregulated DE-miRNAs. qRT-PCR proved that the expression levels of miRNA-18a-5p, miRNA-18b-5p, miRNA-449c-5p and miRNA-1224-5p and their target genes (NR3C1, CTGF, MYC, and TNS1) were consistent with our predictions. Univariate and multivariate Cox proportional hazards regression analyses of the hub genes revealed a significant prognostic value of NR3C1, EZH2, AND GATA4, and these genes were closely related to eight types of immune infiltration cells.Conclusion: We identified three genes as candidate biomarkers for EC, which may provide a theoretical basis for targeted therapy.Keywords: TCGA, endometrial cancer, miRNA-mRNA network, prognostic model, immune infiltration cell

Wei Luo,1,* Ruifen Sun,2,* Xin Chen,3,* Ju Li,4 Jike Jiang,4 Yuxiao He,4 Shaoqing Shi,2 Heling Wen5 1Department of Respiratory and Critical Care Medicine, The People’s Hospital of Leshan, Leshan, Sichuan, People’s Republic of China; 2Center for Scientific Research, Yunnan University of Chinese Traditional Medicine, Kunming, Yunnan, People’s Republic of China; 3College of Chinese Medicine, Yunnan University of Chinese Medicine, Kunming, Yunnan, People’s Republic of China; 4College of Basic Medicine, Yunnan University of Chinese Medicine, Kunming, Yunnan, People’s Republic of China; 5Department of Cardiology, Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital, Chengdu, Sichuan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Heling WenDepartment of Cardiology, Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital, No. 32th West Second Section First Ring Road, Qingyang District, Chengdu, Sichuan 610072, People’s Republic of ChinaTel/Fax +86-28-87394174Email wenheling2008@163.comShaoqing ShiCenter for Scientific Research, Yunnan University of Chinese Traditional Medicine, No. 1076th Yuhua Road, Chenggong District, Kunming, Yunnan 650500, People’s Republic of ChinaTel +86-871-65918050Fax +86-871-65918049Email sqs621@yeah.netIntroduction: The incidence and mortality rates of lung cancer rank top in the different types of cancers in China. Licochalcone A (LA) is a flavonoid extracted from the roots of licorice with antitumor effects in various cancers in vitro and in vivo. However, the role of LA in non-small cell lung cancer (NSCLC) remains largely unclear.Methods: The cell viability was measured by MTT assay, Edu staining and colony formation assay. Apoptosis was investigated using Annexin V/PI double-stained assays with flow cytometry. Real-time quantitative RT-PCR was carried out to investigate the expression of mRNA of related proteins. Western blotting was used to investigate the expression of related proteins.Results: The results show that LA inhibits the proliferation of NSCLC cells in a dose-dependent manner and induces apoptotic cell death. Moreover, LA significantly suppresses the expression of c-IAP1, c-IAP2, XIAP, Survivin, c-FLIPL and RIP1 without influencing the level of mRNA. Cycloheximide chase assay demonstrates that LA greatly decreases the stability of Survivin, XIAP and RIP1. Mechanistic studies indicate that LA induces cytoprotective autophagy since block of autophagy with CQ greatly enhances LA-induced anticancer activities. Furthermore, LA rapidly induces ERK and p38 activation in a time-dependent manner in both A549 and H460 cells, but suppresses the activities of c-Jun N-terminal kinase (JNK); suppression of ERK not p38 with inhibitor attenuates LA-induced autophagy, while it remarkably enhances LA-induced cytotoxicity in lung cancer cells and further promotes the degradation of apoptosis-related proteins.Discussion: The results of this study provide novel insights on the role of apoptosis-related proteins and the MAPKs pathway in the anticancer activities of LA.Keywords: non-small cell lung cancer, NSCLC, licochalcone A, LA, inhibitors of apoptosis proteins, IAPs, RIP1, ERK, autophagy

Bo Yuan,1 Rongqing Sun,1 Yuming Du,1 Zhankui Jia,2 Wencheng Yao,2 Jinjian Yang2 1Intensive Care Unit, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province 450052, People’s Republic of China; 2Urinary Surgery Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province 450052, People’s Republic of ChinaCorrespondence: Jinjian YangUrinary Surgery Department, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Erqi District, Zhengzhou, Henan Province 450052, People’s Republic of ChinaEmail yangjj_2011@126.comObjective: Long non-coding RNA (lncRNA) cancer susceptibility candidate 9 (CASC9) has been reported to play a vital role in tumorigenesis. This study explored the biological role of CASC9 and its regulation mechanism in bladder cancer (BC).Methods: Gene expression was evaluated using quantitative reverse transcription polymerase chain reaction and Western blot. The functional role of CASC9 in BC was studied using Cell Counting Kit-8, colony formation assay, scratch wound healing assay, transwell invasion assay, and xenograft tumor assay. In addition, the mechanism of CASC9 function in BC was determined using RNA immunoprecipitation assay and chromatin immunoprecipitation assay.Results: CASC9 was upregulated in BC tissues and cell lines, and correlated with the staging and metastasis in BC. Knockdown of CASC9 inhibited the proliferation, migration, and invasion of BC cells. Similarly, silencing of CASC9 inhibited tumor growth in vivo. Signal transducer and activator of transcription 3 (STAT3) was upregulated in BC tissues and cell lines, and positively correlated with CASC9 in BC tissues. Moreover, CASC9 was shown to be regulated by STAT3 in BC cells. Furthermore, CASC9 regulated phosphatase and tensin homolog (PTEN) expression by interacting with enhancer of zeste homolog 2 (EZH2). More significantly, CASC9 silencing-mediated inhibition of BC progression was partly reversed by EZH2 overexpression or PTEN inhibition.Conclusion: Upregulation of CASC9 induced by STAT3 promoted the progression of BC by interacting with EZH2 and affecting the expression of PTEN, representing a novel regulatory mechanism for BC progression.Keywords: bladder cancer, cancer susceptibility candidate 9, signal transducer and activator of transcription 3, phosphatase and tensin homolog, enhancer of zeste homolog 2

Hongmei Luo,1,* Ruixue Sun,1,* Yuhuan Zheng,1,2,* Jingcao Huang,1 Fangfang Wang,1 Dan Long,3 Yu Wu1 1Department of Hematology, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2State Key Laboratory of Biotherapy and Cancer Center, Sichuan University, Chengdu, People’s Republic of China; 3Key Laboratory of Transplant Engineering and Immunology, West China Hospital, Sichuan University, Chengdu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yu Wu Tel +86-28-85422370Fax +86-28-85423921Email wu_yu@scu.edu.cnPurpose: Acute myeloid leukemia (AML) is associated with a poor overall prognosis. PIM family genes, including PIM1, PIM2, and PIM3, are proto-oncogenes that are aberrantly overexpressed in different types of human cancers. In this study, we aimed to explore and clarify the function of PIM3 in AML.Patients and Methods: The expression of the three PIM genes in AML was detected using the Gene Expression Omnibus. The expression of PIM3 and PIM3 in patient samples and AML cell lines was measured using quantitative real-time polymerase chain reaction or Western blot analyses. The cellular behaviors of PIM3-overexpressing AML cell lines were detected using a CCK-8 assay, flow cytometry, Western blotting, immunofluorescence staining, and a cell migration assay. The interactions between PIM3 and phosphorylated CXCR4 (pCXCR4) were explored via immunoprecipitation.Results: Higher PIM3 expression was detected in primary AML cells than in healthy donor cells. Second, PIM3 overexpression promoted AML cell proliferation and protected against spontaneous apoptosis by phosphorylating BAD (pBAD) at Ser112. Furthermore, PIM3 overexpression might promote the migration of AML cells via CXCR4. PIM3-overexpressing AML cell lines exhibited increased CXCR4 phosphorylation at Ser339, and pCXCR4 interacted with PIM3.Conclusion: Our findings suggest that PIM3 regulates the proliferation, survival, and chemotaxis of AML cell lines. Moreover, pCXCR4 might mediate the regulation of PIM3-induced chemotaxis. Therefore, the inhibition of PIM3 expression may be a promising therapeutic target in AML.Keywords: pBAD, pCXCR4, PIM1, PIM2, PIM3

Yang Yang,1 Dan Li,2 Yulong Li,3 Qiuyu Jiang,4 Ruifang Sun,5 Jinren Liu,1 Fei Wu,4 Jiyu Miao,4 Lei Ni,4 Xingmin Shi,1 Chen Huang4 1Department of Toxicology and Sanitary Analysis, School of Public Health, Xi’an Jiaotong University Health Science Center, Xi’an 710061, People’s Republic of China; 2Department of Clinical Medicine, Medical College of Yan’an University, Yan’an 716000, Shanxi Province, People’s Republic of China; 3Department of Gastroenterology, Shaanxi Provincial People’s Hospital, Xi’an 710068, People’s Republic of China; 4Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, Xi’an Jiaotong University, Xi’an 710061, People’s Republic of China; 5Department of Pathology, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, Xi’an Jiaotong University, Xi’an 710061, People’s Republic of ChinaCorrespondence: Xingmin ShiSchool of Public Health, Xi’an Jiaotong University Health Science Center, Yanta Western Road 76, Xi’an 710061, People’s Republic of ChinaEmail shixingmin142@163.comChen HuangXi’an Jiaotong University Health Science Center, Yanta Western Road 76, Xi’an 710061, People’s Republic of ChinaTel +86-29-82655077Email hchen@mail.xjtu.edu.cnAim: Low-temperature plasma (LTP) has potential applications in cancer therapy. Herein, we explored the molecular mechanisms of proliferation inhibition induced by LTP.Methods: LTP was generated by a helium atmospheric-pressure plasma jet and used to treat A549 and H1299 cells. CCK-8 and cell apoptosis assays were performed to evaluate the effects of LTP treatment on A549 and H1299 cells. The qRT-PCR was performed to measure the expression of miR-203a after treating with LTP. CCK-8, colony formation,cell apoptosis assays, and Western blotting were performed to analyse the function of miR-203a in the development of lung cancer. Dual-luciferase assay and Western blotting were used to probe the relationship between miR-203a and BIRC5, and gene silencing using si-BIRC5 was carried out to explore the effect of knocking downBIRC5 on lung cancer cells.Results: We found that LTP significantly suppressed proliferation and promoted apoptosis in A549 and H1299 cells. The miR-203a expression was increased after cells were treated with LTP. The miR-203a expression was downregulated among lung cancer tissue samples, and overexpression of miR-203a suppressed cell growth and induced apoptosis in lung cancer cells. We showed that miR-203a targeted BIRC5. Moreover, silencing of BIRC5 caused proliferation inhibition and induced apoptosis in lung cancer cells.Conclusion: Our study revealed that LTP inhibited proliferation and induced apoptosis in A549 and H1299 cells through the miR-203a/BIRC5 axis. These findings showed that LTP could potentially be used to treat lung cancer.Keywords: low-temperature plasma, lung cancer, proliferation, miR-203a, BIRC5

Longyan Yang,1,* Yan Wang,1,* Rongxin Sun,1,* Yuanyuan Zhang,1 Ying Fu,1 Zhaohui Zheng,1 Zhili Ji,2 Dong Zhao1 1Beijing Key Laboratory of Diabetes Research and Care, Center for Endocrine Metabolism and Immune Diseases, Luhe Hospital Capital Medical University, Beijing 101149, People’s Republic of China; 2Department of General Surgery, Luhe Hospital Capital Medical University, Beijing 101149, People’s Republic of China*These authors contributed equally to this workCorrespondence: Dong Zhao; Zhili Ji Tel +86-10-69543901Fax +86-10-69531069Email zhaodong@ccm.edu.cn; lhyyjzl@163.comPurpose: Although papillary thyroid carcinoma (PTC) is associated with a generally favorable prognosis, about 15% of patients present recurrence and distant metastasis in the next decade leading to death. Angiopoietin-like 4 (ANGPTL4) is secreted to circulation and belongs to the angiopoietin-like proteins. The expression of ANGPTL4 was increased in several solid tumor tissues compared to corresponding paracancerous tissues. ANGPTL4 was identified as pro-tumorigenic protein, including stimulating tumor cell growth, promoting tumor metastasis. However, the clinical significance and biological function of ANGPTL4 in PTC is still unclear. Hence, the purpose of this study was to evaluate the role of ANGPTL4 in PTC, investigating the possibility of whether ANGPTL4 could become a novel target for PTC therapy.Methods: We investigated the expression level of ANGPTL4 and pAKT in PTC and paracancerous tissue by immunohistochemistry. We determined the effect of ANGPTL4 in PTC cell proliferation through cell counting kit-8 (CCK-8) and cell cycle by flow cytometry analysis. Furthermore, the correlation between ANGPTL4 expression levels and PTC cell proliferation from the TCGA data set was analyzed by GSEA. We explored the role of ANGPTL4 on the phosphorylation of AKT and proliferation in PTC cells via overexpression or knockdown assays and AKT inhibitor assay.Results: In the present study, we found that ANGPTL4 was highly expressed in both protein and mRNA level in PTC compared with adjacent noncancerous tissues or benign nodule. ANGPTL4 expression increased according to thyroid tumor progression. ANGPTL4 level was positively correlated with the size of PTC. ANGPTL4 increased cell proliferation and decreased cell cycle arrest of PTC. Knockdown of ANGPTL4 inhibited the phosphorylation of AKT. ANGPTL4 regulated PTC cell proliferation through AKT signaling pathway.Conclusion: Our findings suggested that ANGPTL4 was increased in PTC compared with adjacent noncancerous tissues, and ANGPTL4 increased cell proliferation and inhibited cell cycle arrest in PTC cells via promoting AKT phosphorylation. The study may provide fundamental information to suggest its suitability as a target for the treatment of PTC.Keywords: papillary thyroid carcinoma, angiopoietin-like 4, AKT, proliferation

Ruimei Sun,1 Xiujiang Sun,2 Hua Liu,3 Peirui Li2 1Department of Radiotherapy, The Affiliated Hospital of Weifang Medical University, Weifang 261041, People’s Republic of China; 2Department of Thyroid and Breast Surgery, The Affiliated Hospital of Weifang Medical University, Weifang 261041, People’s Republic of China; 3Department of Gynaecology, The Affiliated Hospital of Weifang Medical University, Weifang 261041, People’s Republic of ChinaCorrespondence: Peirui LiDepartment of Thyroid and Breast Surgery, The Affiliated Hospital of Weifang Medical University, No. 2428, Yuhe Road, Weifang 261041, People’s Republic of ChinaTel +86-0536-3081399Email lipeirui536@sina.comBackground and objective: Endometrial carcinoma (EC) is one of the most frequently diagnosed malignancies in females. Dysregulation of lncRNA TDRG1 has been widely documented in several cancers, including EC. However, the mechanism of this lncRNA involving in EC progression remains to be further elucidated.Materials and methods: The enrichment levels of TDRG1 in EC tissues and cell lines were examined by RT-qPCR. Flow cytometry, cell counting kit-8 (CCK-8), transwell, and Western blot assays were conducted to assess whether TDRG1 knockdown could affect cell cycle arrest, proliferation, migration, invasion, and apoptosis of EC cells. The phosphorylation levels of mTOR, AKT and PI3K that associated with PI3K/Akt/mTOR pathway were determined by Western blot assay.Results: TDRG1 expression was markedly upregulated in EC tissues and cell lines. Knockdown of TDRG1 significantly induced cell cycle arrest and apoptosis, inhibited cell proliferation, restrained the invasion and migration abilities in EC cells. Moreover, TDRG1 silencing decreased the protein levels of p-AKT, p-PI3K, and p-mTOR of EC cells.Conclusion: Our data underlined the implication of TDRG1 in EC progression, proposing that targeting TDRG1 might be a potential therapeutic avenue in EC.Keywords: endometrial carcinoma, TDRG1, PI3K/AKT/mTOR pathway

Hongwei Guan,1,* Juan Li,1,* Rui Sun,1 Wei Liu,1 Mei Feng,2 Hui Ma,3 Changzhong Li1 1Department of Obstetrics and Gynecology, Shandong Provincial Hospital affiliated to Shandong University, Jinan, People’s Republic of China; 2Central Laboratory, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, People’s Republic of China; 3Shandong University of Traditional Chinese Medicine, Jinan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Changzhong LiDepartment of Obstetrics and Gynecology, Shandong Provincial Hospital affiliated to Shandong University, 324 Jingwuweisi Road, Jinan 250021, People’s Republic of ChinaTel +86 531 15168888909Email 15168888909@163.comPurpose: The aim of our research was to investigate the expression of BMP7 in ovarian cancer (OC) and the biological effect of knocking down BMP7 on ovarian cancer A2780 cells.Methods: We detected BMP7 expression in ovarian cancer and normal ovarian tissue by immunohistochemistry (IHC). We downregulated BMP7 expression using lentivirus-mediated RNAi and then examined the effects of knocking down BMP7 on the cell growth and invasion, cell cycle and paclitaxel sensitivity of A2780 cells. The mRNA and protein levels were detected by total RNA extraction and quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting, respectively. Cell proliferation was measured by CCK-8 and colony formation assays. The number of cells in each cell cycle stage and those undergoing apoptosis were measured by flow cytometry.Results: BMP7 expression was significantly higher in the ovarian cancer tissues than it was in the normal ovarian tissues. Knocking down BMP7 in ovarian cancer A2780 cells inhibited cell proliferation, migration and invasion; led to G1 cell cycle arrest; and reversed the epithelial-mesenchymal transformation (EMT) process. In addition, downregulating BMP7 increased the sensitivity of the A2780 cells to paclitaxel. Moreover, BMP7 downregulation resulted in decreased expression of Smad1/5/9, p-Smad1/5/9, ID2 and cyclin D1 protein.Conclusion: The results presented here are expected to contribute to the development of possible therapeutic targets for patients with ovarian cancer.Keywords: BMP7, ovarian cancer, EMT, drug sensitivity, proliferation, cell cycle

Du Meng,1,* Hongwei Lei,2,* Xiaoqiang Zheng,3 Yaxuan Han,4 Ronggang Sun,5 Dongli Zhao,1 Rui Liu11Department of Radio Oncology, The First Affiliated Hospital of Xi’an Jiaotong University School of Medicine, Xi’an, Shaanxi Province, 710061, People’s Republic of China; 2Department of Radio Oncology, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning Province, 116027, People’s Republic of China; 3Department of Medical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University School of Medicine, Xi’an, Shaanxi Province, 710061, People’s Republic of China; 4Department of Oncology, The Xi’an Chest Hospital, Xi’an, Shaanxi Province, 710000, People’s Republic of China; 5Department of Radio Oncology, The People’s Hospital of YangZhong City, YangZhong, Jiangsu Province, 212200, People’s Republic of China*These authors contributed equally to this workBackground: Breast cancer is one of the foremost threats to female health nowadays. Tamoxifen, an antagonist of estrogen receptor-α (ERα), is the first choice for endocrine-dependent breast cancer (ERα-positive breast cancer) treatment. However, ERα has an important function in the normal physical regulation of estrogen, and current oral administration of tamoxifen has potential side effects on normal endocrine secretion. In the present work, we aim to develop novel approaches to increase the antitumor effect of tamoxifen on breast cancer cells and decrease the potential side effects in the human body during treatment.Methods: A temperature-sensitive phase-change hydrogel for tamoxifen (Tam-Gel) was generated. After establishing subcutaneous tumors formed by MCF-7, an ERα-positive breast cancer cell line, in nude mice, an intratumoral injection of Tam-Gel was performed to examine whether Tam-Gel facilitated the slow-release or antitumor effect of tamoxifen. A metastatic breast cancer model was established using the intrahepatic growth of MCF-7 cells in immunodeficient rats.Results: Tam-Gel can transform from liquid to hydrogel at room temperature. An intratumoral injection of Tam-Gel facilitated the slow-release or antitumor effect of tamoxifen. Once Tam-Gel, but not Tam-Sol, was administered by intratumoral injection, it significantly decreased the uptake of radionuclide probes (18F-fluoroestradiol or 18F-fluorodeoxyglucose) by cells in rats’ livers and the intrahepatic growth of MCF-7 cells in rats’ livers.Conclusion: A novel slow-release system was successfully prepared to facilitate the long-term release of tamoxifen in breast cancer tissues, and achieved an antitumor effect in the long term.Keywords: breast cancer, estrogen receptor-α, tamoxifen nanoparticle, temperature-sensitive phase-change hydrogel

Ruilin Sun,1 Xi Lu,1 Li Gong,2 Faguang Jin1 1Department of Respiratory Medicine, The Second Affiliated Hospital of Air Force Medical University, Xi’an, People’s Republic of China; 2Department of Pathology, The Second Affiliated Hospital of Air Force Medical University, Xi’an, People’s Republic of China Background: Lung cancer is the most common and lethal malignancy worldwide. TCTP is highly expressed in various cancers including lung cancer. Epithelial–mesenchymal transition (EMT) could increase cancer cell invasion. Whether TCTP’s expression is associated with EMT in lung adenocarcinoma is largely unknown.Methods: Several Gene Expression Omnibus datasets were used to analyze the correlation between TCTP expression and overall survival of lung adenocarcinoma patients by Kaplan–Meier survival analysis. Then, 24 surgically removed fresh lung adenocarcinoma tissue samples and paired paracancer tissue samples were used to analyze the correlation between TCTP expression and tumor stage by immunohistochemical analysis. Furthermore, stable cell lines were generated using lentiviral transduction systems to knock down or overexpress TCTP in A549 cells. Cell migration and invasion were measured by scratch and transwell assays, and EMT marker proteins such as α-SMA, ZEB1, and E-cadherin were quantitated by Western blot. The expression levels of miR-200a, miR-141, and miR-429 were determined by real-time quantitative PCR, and their target genes were predicted by an online database miRTarBase. The interaction between TCTP and these genes was analyzed by String database and visualized by Cytoscape.Results: TCTP was highly expressed in tumor tissues compared to paracancer tissues. The expression of TCTP was associated with shorter overall survival. TCTP knockdown experiment in A549 cells suggested that TCTP knockdown could decrease the migration and invasion of lung cancer cells, and the expression level of ZEB1 and α-SMA, but increase the expression of E-cadherin and p53. Vice versa, overexpression of TCTP could increase the migration and invasion of cancer cells, and the expression level of ZEB1 and α-SMA, but decrease the expression of E-cadherin and p53. Furthermore, we found the expression of miR-200a, miR-141, and miR-429 was associated with TCTP expression.Conclusion: TCTP promotes EMT in lung adenocarcinoma, and this effect may be associated with miR-200 family members like miR-200a, miR-141, and miR-429. Keywords: TCTP, lung adenocarcinoma, epithelial–mesenchymal transition, miR-200

Chun-li Gao,1,* Rui Sun,2,* Dong-hai Li,3 Fei Gong1 1Department of Gastroenterology, 2Department of Oncology, 3Department of Pathology, The First People’s Hospital of Lanzhou City, Lanzhou, Gansu, 730050, China *These authors contributed equally to this work Background: PIWI-like protein 1 (PIWIL1) is an important member of the Argonaute protein family and is closely related to the malignant behaviors of tumor cells. This study aimed to investigate the relationship between PIWIL1 and gastric cancer (GC). Methods: We investigated PIWIL1 expression status in GC tissues as well as its association with clinicopathological characteristics and prognosis of GC patients. PIWIL1 siRNA was transfected into a GC cell line to elucidate its impact on malignant biological behavior. Results: The results showed that PIWIL1 was upregulated in GC tissues and correlated with tumor differentiation, lymph node status, and TNM stage. The high PIWIL1 expression was an independent predictor for the prognosis of patients with GC. Silencing of PIWIL1 expression in GC cell lines suppressed tumor cell proliferation, migration, and invasion. Conclusion: High PIWIL1 expression suggests a poor prognosis for GC patients and PIWIL1 can serve as an important molecular marker for predicting the prognosis of GC patients. Keywords: gastric cancer, PIWIL1, invasion, metastasis

Rongxin Sun,1,2 Aikeremujiang Muheremu,3 Yihe Hu1 1Department of Orthopedics, Xiangya Hospital, CentralSouth University, Kaifu District, Changsha, Hunan 86410008, China; 2Department of Orthopedics, Sixth Affiliated Hospital of Xinjiang Medical University, Tianshan District, Urumqi, Xinjiang 86830001, China; 3Department of Spine Surgery, Sixth Affiliated Hospital of Xinjiang Medical University, Tianshan District, Urumqi, Xinjiang 86830001, China Objective: Osteosarcoma is a highly malignant osseous sarcoma with poor prognosis. Previous studies indicated that miRNA-30c may play an important role in the development of osteosarcoma, but its mechanism is not yet clear. The current research was carried out to explore the potential applications of miR-30c in the diagnosis and treatment of osteosarcoma.Materials and methods: Real-time PCR and in situ hybridization were used to test the correlation between miR-30c and the onset of osteosarcoma. In vitro transfection of miR-30 mimic was used to test the effect of miR-30c on the development of osteosarcoma. Cell Counting Kit-8, formation of Petri dish clones, in vivo formation of tumor, flow cytometry tests and Transwell analysis were used to assess the effect of miR-330c on the metastatic potential and invasiveness of osteosarcoma.Results: Reverse transcriptase-PCR analysis and in situ hybridization tests revealed that the expression of miR-30c was lower in the osteosarcoma tissue than in normal bone tissue (P

Ting Li, Ruochuan Sun, Mingdian Lu, Jiacong Chang, Xiangling Meng,* Huo Wu* Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, He Fei, 230222, China *These authors contributed equally to this work Background: NDRG3 is an N-myc downregulated gene (NDRG). The aim of this article was to identify the role of NDRG3 in colorectal cancer (CRC) and to determine the mechanism underlying its function. Methods: Using immunohistochemical staining, expression and clinicopathological variables of NDRG3 were analyzed in 170 CRC samples. Overexpression of NDRG3 was employed in SW1116 cells, downregulation of NDRG3 was achieved in RKO cells, then migration and invasion assays were performed in vitro, and a mouse model was constructed in vivo. Results: Increased expression of NDRG3 was observed in primary CRC tissues, and this expression was correlated with distant metastasis. Consistently, ectopic expression of NDRG3 in SW1116 cells enhanced cell migration and invasion, while knockdown of NDRG3 in RKO cells significantly suppressed CRC cell metastasis. The portal vein injection models suggested that NDRG3 overexpression facilitates liver metastasis. These events were associated with the phosphorylation of Src (c-Src) at Tyr 419 site. Conclusion: Our results showed that NDRG3 facilitates CRC migration and invasion by activating Src phosphorylation, suggesting the role of NDRG3 as a candidate oncogene. Keywords: NDRG3, colorectal cancer, metastasis, Src

Ying Liu,1,2,* Baocun Sun,1–3,* Tieju Liu,1,2,* Xiulan Zhao,1,2 Xudong Wang,3 Yanlei Li,1,2 Jie Meng,2 Qiang Gu,1,2 Fang Liu,1,2 Xueyi Dong,1,2 Peimei Liu,2 Ran Sun,2 Nan Zhao1 1Department of Pathology, General Hospital of Tianjin Medical University, 2Department of Pathology, Tianjin Medical University, 3Department of Pathology, Cancer Hospital of Tianjin Medical University, Tianjin, People’s Republic of China *These authors contributed equally tothis work Abstract: Tumor cell vasculogenic mimicry (VM), a newly defined pattern of tumor blood supply, signifies the functional plasticity of aggressive cancer cells forming vascular networks. VM and cancer stem cells (CSCs) have been shown to be associated with tumor growth, local invasion, and distant metastasis. In our previous study, CSCs in triple-negative breast cancer were potential to participate in VM formation. In this study, breast CSCs were isolated from the triple-negative breast cancer cell line MDA-MB-231 by using mammosphere culture. Western blotting and reverse transcription polymerase chain reaction showed that mammosphere cells displayed an increased expression of AURKA protein kinase and stem cell marker c-myc and sox2. The VM formation by mammosphere cells was inhibited by AURKA knockdown or the addition of AURKA inhibitor MLN8237. In the meantime, MLN8237 induced the increased E-cadherin and decreased c-myc, sox2, and β-catenin expressions. The function of AURKA in VM formation was further confirmed using a xenograft-murine model. The results suggested that AURKA protein kinase is involved in VM formation of CSCs and may become a new treatment target in suppressing VM and metastasis of breast cancer. Keywords: AURKA, cancer stem cells, vasculogenic mimicry, breast cancer

Junsheng Gu, Ranran Sun, Shen Shen, Zujiang Yu Department of Infectious Diseases, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan, People’s Republic of China Objective: This study was designed to explore the influence of Toll-like receptor 4 (TLR4) agonist lipopolysaccharides (LPS) on liver cancer cell and the feasibility to perform liver cancer adjuvant therapy. Methods: Human liver cancer cell lines HepG2, H7402, and PLC/PRF/5 were taken as models, and the expression of TLRs mRNA was detected by real time-polymerase chain reaction method semiquantitatively. WST-1 method was used to detect the influence of LPS on the proliferation ability of liver cancer cells; propidium iodide (PI) single staining and Annexin V/PI double staining were used to test the influence of LPS on the cell cycle and apoptosis, respectively, on human liver cancer cell line H7402. Fluorescent quantitative polymerase chain reaction and Western blot method were used to determine the change of expression of Cyclin D1. Results: The results demonstrated that most TLRs were expressed in liver cancer cells; stimulating TLR4 by LPS could upregulate TLR4 mRNA and the protein level, activate NF-κB signaling pathway downstream of TLR4, and mediate the generation of inflammatory factors IL-6, IL-8, and TNF-α; LPS was found to be able to strengthen the proliferation ability of liver cancer cells, especially H7402 cells; the expression of Cyclin D1 rose and H7402 cells were promoted to transit from G1 stage to S stage under the stimulation of LPS, but cell apoptosis was not affected. It was also found that LPS was able to activate signal transducer and activator of transcription -3 (STAT3) signaling pathway in H7402 cells and meanwhile significantly increase the initiation activity of STAT3; proliferation promoting effect of LPS to liver cancer cells remarkably lowered once STAT3 was blocked or inhibited. Conclusion: Thus, TLR4 agonist LPS is proved to be able to induce liver cancer cells to express inflammation factors and mediate liver cancer cell proliferation and generation of multidrug resistance by activating the cyclooxygenase-2/prostaglandin signal axis as well as the STAT3 pathway. Keywords: water soluble tetrazolium-1, propidium iodide single staining, Annexin V/PI double staining, cell proliferation, signaling pathway, LPS

Gu J, Sun R, Shen S, Yu Z. The influence of TLR4 agonist lipopolysaccharides on hepatocellular carcinoma cells and the feasibility of its application in treating liver cancer. Onco Targets Ther. 2015;8:2215–2225.The first author (Junsheng Gu) created an email address for Dr Yu without permission and used figures from a previously published paper: Lin A, Wang G, Zhao H, et al. TLR4 signaling promotes a COX-2/PGE2/STAT3 positive feedback loop in hepatocellular carcinoma (HCC) cells. OncoImmunology. 2015: DOI:10.1080/2162402X.This was done without the knowledge, involvement, or permission of Dr Yu.This retraction relates to this paper