title: hsa-miR-135a-1 inhibits prostate cancer cell growth and migration by targeting EGFR.
abstract: Prostate cancer is one of the leading causes of death in men worldwide. Differentially expressed microRNAs (miRNAs) are associated with metastatic prostate cancer. However, their potential roles for affecting prostate cancer initiation and progression remain largely unknown. Here, we examined the aberrant expression profiles of miRNAs in human metastatic prostate cancer tissues. We further validated our miRNA expression data using two large, independent clinical prostate cancer datasets from the Memorial Sloan Kettering Cancer Center (MSKCC) and The Cancer Genome Atlas (TCGA). Our data support a model in which hsa-miR-135-1 acts as a potential tumor suppressor in metastatic prostate cancer. First, its downregulation was positively correlated with late TNM stage, high Gleason score, and adverse prognosis. Second, cell growth, cell cycle progression, cell migration and invasion, and xenograft tumor formation were dramatically inhibited by miR-135a overexpression. Third, in the microarray gene expression data analysis using Gene Set Enrichment Analysis (GSEA), Database for Annotation, Visualization and Integrated Discovery (DAVID) analysis, Ingenuity Pathway Analysis (IPA), and Oncomine concept analysis, we showed that miR-135a targets multiple oncogenic pathways including epidermal growth factor receptor (EGFR), which we verified using functional experimental assays. These results help advance our understanding of the function of miRNAs in metastatic prostate cancer and provide a basis for further clinical investigation.
authors.affiliation: Department of Urology, Zhongda Hospital, School of Medicine, Southeast University, 87 Dingjia Bridge Hunan Road, Nanjing, 210009, China.|Surgical Research Center, Institute of Urology, Southeast University Medical School, Nanjing, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Xu
authors.affiliation: Department of Urology, Zhongda Hospital, School of Medicine, Southeast University, 87 Dingjia Bridge Hunan Road, Nanjing, 210009, China.|Surgical Research Center, Institute of Urology, Southeast University Medical School, Nanjing, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Tao
authors.affiliation: Department of Urology, Zhongda Hospital, School of Medicine, Southeast University, 87 Dingjia Bridge Hunan Road, Nanjing, 210009, China.|Surgical Research Center, Institute of Urology, Southeast University Medical School, Nanjing, China.
authors.forename: Yiduo
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Immunology, Bengbu Medical College, Bengbu, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Fang
authors.affiliation: Department of Urology, Zhongda Hospital, School of Medicine, Southeast University, 87 Dingjia Bridge Hunan Road, Nanjing, 210009, China.|Surgical Research Center, Institute of Urology, Southeast University Medical School, Nanjing, China.
authors.forename: Yeqing
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Urology, Zhongda Hospital, School of Medicine, Southeast University, 87 Dingjia Bridge Hunan Road, Nanjing, 210009, China.
authors.forename: Shuqiu
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Urology, Zhongda Hospital, School of Medicine, Southeast University, 87 Dingjia Bridge Hunan Road, Nanjing, 210009, China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Zhu
authors.affiliation: Department of Urology, Zhongda Hospital, School of Medicine, Southeast University, 87 Dingjia Bridge Hunan Road, Nanjing, 210009, China. mingchenseu@126.com.|Surgical Research Center, Institute of Urology, Southeast University Medical School, Nanjing, China. mingchenseu@126.com.
authors.forename: Ming
authors.initials: M
authors.lastname: Chen
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D016022:Case-Control Studies; D002453:Cell Cycle; D002465:Cell Movement; D049109:Cell Proliferation; D018450:Disease Progression; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D060787:Neoplasm Grading; D011467:Prostate / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: C544965:MIRN135 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: EGFR; Metastasis; Prostate cancer; miRNA