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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 FEBS+Open+Bio
2015 ; 5
(ä): 900-7
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MicroRNA-431 inhibits migration and invasion of hepatocellular carcinoma cells by
targeting the ZEB1-mediated epithelial-mensenchymal transition
#MMPMID26697292
Sun K
; Zeng T
; Huang D
; Liu Z
; Huang S
; Liu J
; Qu Z
FEBS Open Bio
2015[]; 5
(ä): 900-7
PMID26697292
show ga
MicroRNA-431 (miR-431) has been recognized as an oncogenic miRNA, being
implicated in the initiation and development of human cancers. Recently,
deregulation of miR-431 has been reported in several tumors. However, the
clinical significance of miR-431 and its underlying role in human hepatocellular
carcinoma (HCC) are poorly explored. Herein, we found that miR-431 expression was
reduced in HCC tissues compared to noncancerous tissues. Otherwise,
down-regulation of miR-431 was observed in aggressive tumor tissues. The levels
of miR-431 expression in HCC cell lines were significantly lower than that in a
nontransformed hepatic cell line. Clinical association analyses disclosed that a
low level of miR-431 was prominently associated with poor prognostic features of
HCC including venous infiltration, high Edmondson-Steiner grading and advanced
tumor-node-metastasis (TNM) tumor stage. Our in vitro studies showed that
up-regulation of miR-431 expression reduced cell invasion and migration in HCCLM3
cells. In contrast, down-regulation of miR-431 expression promoted SMMC-7721 cell
invasion and migration. We found that up-regulation of miR-431 expression
decreased zinc finger E-box binding homeobox 1 (ZEB1) expression and inhibited
the epithelial-mesenchymal transition (EMT) with increased E-cadherin expression
and decreased vimentin expression in HCCLM3 cells. Otherwise, down-regulation of
miR-431 expression increased ZEB1 expression and promoted EMT in SMMC-7721 cells.
Significantly, ZEB1 was identified as a target of miR-431 in HCC. ZEB1 knockdown
abrogated the effect of miR-431 silencing on EMT and cell mobility in SMMC-7721
cells. In conclusion, miR-431 inhibits migration and invasion of HCC cells by
suppressing ZEB1-mediated EMT.
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