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Int J Biochem Cell Biol. 2016 Oct;79:249-260. doi: 10.1016/j.biocel.2016.08.043. Epub 2016 Sep 1.

Androgen-induced miR-27A acted as a tumor suppressor by targeting MAP2K4 and mediated prostate cancer progression.

Author information

1
State Key Laboratory of Genetic Engineering, Shanghai Engineering Research Center of Industrial Microorganisms, School of Life Science, Fudan University, Shanghai 200433, PR China.
2
Shanghai Institute of Planned Parenthood Research Hospital, WHO Collaborating Center for Research in Human Reproduction, Shanghai 200433, PR China.
3
State Key Laboratory of Transducer Technology, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Science, Shanghai 200433, PR China. Electronic address: jingfx@mail.sim.ac.cn.
4
State Key Laboratory of Genetic Engineering, Shanghai Engineering Research Center of Industrial Microorganisms, School of Life Science, Fudan University, Shanghai 200433, PR China. Electronic address: yaoli@fudan.edu.cn.

Abstract

Prostate cancer (PCa) is the most commonly diagnosed and secondly leading cause of cancer death among males. But the precise mechanism of prostate cancer progression, including microRNAs (miRNAs) functioning in it, is still needs further study. We found miR-27a to be down-regulated in prostate cancer, and we investigated the mechanism and role of miRNA-27a in prostate cancer. MiR-27a, a transcriptional target of AR, was an androgen-induced miRNA in LNCaP cells. In castration-resistant prostate cancer (CRPC) cells, we for the first time reported that miR-27a was downregulated by PI3K signaling. MiR-27a functioned as a tumor suppressor in prostate cancer. Over-expression of miR-27a decreased prostate cancer cell proliferation and migration, and induced prostate cancer cell cycle arrest and apoptosis. MAP2K4, miR-27a's direct target gene, functioned as an oncogene in prostate cancer by reducing G1-S phase arrest and inhibiting cell apoptosis of prostate cancer cells. In conclusion, miR-27a functions as a tumor suppressor by suppressing MAP2K4 which acts as an oncogene in prostate cancer cell lines; we also provided a new mechanism of castration-resistant prostate cancer mediated by miR-27a that downregulation of miR-27a caused by aberrant AR signaling and PI3K/Akt signaling after androgen deprivation therapy (ADT) would promote the progression of castration-resistant prostate cancer.

KEYWORDS:

ADT; Androgen receptor; CRPC; PI3K signaling; microRNA

PMID:
27594411
DOI:
10.1016/j.biocel.2016.08.043
[Indexed for MEDLINE]

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