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.
International journal of oncology. 2016 Feb 15 [Epub ahead of print]
Peng Zhou, Liang Ma, Jun Zhou, Min Jiang, Enyu Rao, Yong Zhao, Feng Guo
Central Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P. R. China. , Central Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P. R. China. , Central Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P. R. China. , Department of Blood Transfusion, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P. R. China. , State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, P. R. China. , State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, P. R. China. , Central Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P. R. China.