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GATA3-driven expression of miR-503 inhibits prostate cancer progression by repressing ZNF217 expression.

Abstract：

:Although increasing evidence demonstrated that deregulation of mircoRNA-503 (miRNA-503) contributes to tumorigenesis, little is known about the biological role and intrinsic regulatory mechanisms of miR-503 in prostate cancer (PCa). In present study, we found that miR-503 was significantly downregulated in advanced PCa tissues and cell lines. Downregulation of miR-503 was strongly associated with aggressive clinical-pathological features and poor prognosis in PCa patients. Ectopic expression of miR-503 significantly inhibited tumor cells growth, cell migration and invasion in vitro and in vivo. Mechanistic studies revealed that ZNF217 was a direct target downstream target of miR-503. Knockdown of ZNF217 mimicked the tumor-suppressive effects of miR-503 overexpression on PCa invasion, whereas ZNF217 overexpression attenuated the tumor-suppressive function of miR-503. Subsequently, miR-503 further modulated the activation of ZNF217-downstream epithelial-mesenchymal transition (EMT) genes. Besides, we also found that GATA3 directly increased miR-503 expression and thus decreased ZNF217 expression, indicating the involvement of GATA3/miR-503/ZNF217 signaling in EMT process. Collectively, our results demonstrated that GATA3-driven expression of miR-503 inhibits PCa progression by repressing ZNF217 expression, and also implicated the potential application of miR-503 in PCa therapy.

journal_name

Cell Signal

journal_title

Cellular signalling

authors

Jiang X,Chen Y,Du E,Yang K,Zhang Z,Qi S,Xu Y

doi

10.1016/j.cellsig.2016.06.002

subject

Has Abstract

pub_date

2016-09-01 00:00:00

pages

1216-24

issue

9

eissn

0898-6568

issn

1873-3913

pii

S0898-6568(16)30137-1

journal_volume

28

pub_type

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