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- Title
MicroRNA-431 inhibits migration and invasion of hepatocellular carcinoma cells by targeting the ZEB1-mediated epithelial–mensenchymal transition.
- Authors
Sun, Kexin; Zeng, Tiancai; Huang, Dong; Liu, Zizhong; Huang, Shang; Liu, Jiong; Qu, Zhenfan
- Abstract
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.
- Subjects
LIVER cancer; ZINC-finger proteins; MICRORNA genetics; CANCER invasiveness; CANCER cell migration; EPITHELIAL cells; CELL transformation; PREVENTION
- Publication
FEBS Open Bio, 2015, Vol 5, p900
- ISSN
2211-5463
- Publication type
Article
- DOI
10.1016/j.fob.2015.11.001