MiR-199a-3p promotes gastric cancer progression by targeting ZHX1.

Abstract:

:Accumulating evidence has indicated that microRNAs (miRNAs) act as critical epigenetic regulators in tumor carcinogenesis. Here, we report that miR-199a-3p was significantly upregulated in gastric cancer (GC) cell lines and tissues. Functional studies demonstrated that miR-199a-3p dramatically increased cell proliferation and suppressed cell apoptosis both in vitro and in vivo. Furthermore, the transcriptional regulator zinc fingers and homeoboxes 1 (ZHX1) was identified as one of the direct downstream targets of miR-199a-3p, miR-199a-3p bound to the ZHX1 3′ untranslated region (3′UTR) to regulate ZHX1 protein expression. In addition, the expression of miR-199a-3p was inversely associated with that of ZHX1 in GC cell lines. Overexpression of miR-199a-3p in SGC-7901 cells inhibited ZHX1 expression, while reduction in miR-199a-3p by inhibitors in NCI-N87 cells enhanced ZHX1 expression. Moreover, restoring ZHX1 expression in SGC-7901/miR-199a-3p cells inhibited the cell proliferation induced by miR-199a-3p. Taken together, these findings suggest that miR-199a-3p may function as a novel tumor promoter in GC and its oncogenic activity may involve the direct targeting and inhibition of ZHX1.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Wang Z,Ma X,Cai Q,Wang X,Yu B,Cai Q,liu B,Zhu Z,Li C

doi

10.1016/j.febslet.2014.09.047

subject

Has Abstract

pub_date

2014-11-28 00:00:00

pages

4504-12

issue

23

eissn

0014-5793

issn

1873-3468

pii

S0014-5793(14)00768-6

journal_volume

588

pub_type

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