title: miR-17-92 plays an oncogenic role and conveys chemo-resistance to cisplatin in human prostate cancer cells.
abstract: The mir-17-92 cluster consists of six mature miRNAs and is implicated in diverse human cancers by targeting mRNAs involved in distinct pathways that either promote or inhibit carcinogenesis. However, the molecular mechanism underlying the mir-17-92 cluster-mediated pro-tumorigenic or anti-tumorigenic effects has not been clearly elucidated in prostate cancer. In the present study, the role of the mir-17-92 cluster in diverse aspects of prostate cancer cells has been thoroughly investigated. Forced introduction of the mir-17-92 cluster into the androgen-independent DU145 prostate cancer cells evidently promoted cell growth due to disruption of the balance between cellular proliferation and apoptosis. Overexpression of the mir-17-92 cluster significantly improved the migration and invasion of the DU145 cells, attributed to the induction of integrin β-1. Notably, the mir-17-92 cluster conveyed chemo-resistance to cisplatin. We demonstrated that the mir-17-92 cluster suppressed the expression of inhibitor of the AKT signaling pathway and activated the AKT pathway subsequently, which played a central role in regulating cellular proliferation, apoptosis and chemo-resistance. Continuously activated ERK1/2 signaling also contributed importantly to these processes. The present study provides key evidence for crucial oncogenic role of the miR-17-92 cluster in prostate cancer cells. Further investigations are warranted to determine whether miR-17-92 cluster can be targeted for future treatment of human prostate cancer.
authors.affiliation: Central Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhou
authors.affiliation: Central Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
authors.forename: Liang
authors.initials: L
authors.lastname: Ma
authors.affiliation: Central Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Blood Transfusion, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, P.R. China.
authors.forename: Enyu
authors.initials: E
authors.lastname: Rao
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, P.R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Central Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Guo
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002945:Cisplatin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D062085:RNA, Long Noncoding
chemical_list: D019012:Integrin beta1; C568997:MIR17HG, human; D035683:MicroRNAs; D062085:RNA, Long Noncoding; D002945:Cisplatin