Published in:
Open Access
01-12-2016 | Primary research
miRNA-135a promotes hepatocellular carcinoma cell migration and invasion by targeting forkhead box O1
Authors:
Yue-Bin Zeng, Xing-Hua Liang, Guang-Xian Zhang, Nan Jiang, Tong Zhang, Jian-Ying Huang, Lei Zhang, Xian-Cheng Zeng
Published in:
Cancer Cell International
|
Issue 1/2016
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Abstract
Aims
Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality worldwide. Many microRNAs (miRNAs), small non-coding RNAs, are involved in regulating cancer cell proliferation, metastasis, migration, invasion and apoptosis.
Main methods
We investigated the expression of miR-135a in HCC cell lines and clinical tissues. The effect of miR-135a on migration and invasion of HepG2 and MHCC-97L were examined using wound healing and Transwell assay. We determined the expression of miR-135a, forkhead box O1 (FOXO1), matrix metalloproteinase-2 (MMP-2) and Snail using real-time PCR and western blotting.
Key findings
We found miR-135a was upregulated in HCC cell lines and tissues. miR-135a overexpression promoted HCC cells migration and invasion, whereas miR-135a inhibition suppressed HCC cells migration and invasion. miR-135a overexpression could upregulate the expression of MMP2, Snail and the phosphorylation of AKT, but decreased FOXO3a phosporylation. Tumor suppressor FOXO1 was the direct target for miR-135a.
Significance
Our results suggested that miR-135a might play an important role in promoting migration and invasion in HCC and presents a novel mechanism of miRNA-mediated direct suppression of FOXO1 in HCC cells.