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MicroRNA-7 inhibits the stemness of prostate cancer stem-like cells and tumorigenesis by repressing KLF4/PI3K/Akt/p21 pathway.


ABSTRACT: Up to now, the molecular mechanisms underlying the stemness of prostate cancer stem cells (PCSCs) are still poorly understood. In this study, we demonstrated that microRNA-7 (miR-7) appears to be a novel tumor-suppressor miRNA, which abrogates the stemness of PCSCs and inhibits prostate tumorigenesis by suppressing a key stemness factor KLF4. MicroRNA-7 is down-regulated in prostate cancer cells compared to non-tumorigenic prostate epithelial cells. Restoration of miR-7 suppresses the expression of the stemness factor KLF4 in PCSCs and inhibits prostate tumorigenesis both in vitro and in vivo. Interestingly, the suppression of the stemness of PCSCs by miR-7 is sustained for generations in xenografts. Analysis of clinical samples also revealed a negative correlation between miR-7 expression and prostate tumor progression. Mechanistically, overexpression of miR-7 may lead to a cell cycle arrest but not apoptosis, which seems achieved via suppressing the KLF4/PI3K/Akt/p21 pathway. This study identifies miR-7 as a suppressor of PCSCs' stemness and implicates its potential application for PCa therapy.

SUBMITTER: Chang YL 

PROVIDER: S-EPMC4695167 | biostudies-other | 2015 Sep

REPOSITORIES: biostudies-other

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MicroRNA-7 inhibits the stemness of prostate cancer stem-like cells and tumorigenesis by repressing KLF4/PI3K/Akt/p21 pathway.

Chang Yun-Li YL   Zhou Pei-Jie PJ   Wei Lianzi L   Li Wang W   Ji Zhongzhong Z   Fang Yu-Xiang YX   Gao Wei-Qiang WQ  

Oncotarget 20150901 27


Up to now, the molecular mechanisms underlying the stemness of prostate cancer stem cells (PCSCs) are still poorly understood. In this study, we demonstrated that microRNA-7 (miR-7) appears to be a novel tumor-suppressor miRNA, which abrogates the stemness of PCSCs and inhibits prostate tumorigenesis by suppressing a key stemness factor KLF4. MicroRNA-7 is down-regulated in prostate cancer cells compared to non-tumorigenic prostate epithelial cells. Restoration of miR-7 suppresses the expression  ...[more]

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