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Molecular Cancer
Published in: Molecular Cancer 1/2017

Open Access 01-12-2017 | Research

MicroRNA-1296 inhibits metastasis and epithelial-mesenchymal transition of hepatocellular carcinoma by targeting SRPK1-mediated PI3K/AKT pathway

Authors: Qiuran Xu, Xin Liu, Zhikui Liu, Zhenyu Zhou, Yufeng Wang, Jianfeng Tu, Lijie Li, Hangxing Bao, Liu Yang, Kangsheng Tu

Published in: Molecular Cancer | Issue 1/2017

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Abstract

Background

Increasing evidences demonstrate that miRNAs contribute to development and progression of hepatocellular carcinoma (HCC). Underexpression of miR-1296 is recently reported to promote growth and metastasis of human cancers. However, the expression and role of miR-1296 in HCC remain unknown.

Methods

The levels of miR-1296 in HCC tissues and cells were detected by qRT-PCR. Immunoblotting and immunofluorescence were used for detection of epithelial-to-mesenchymal transition (EMT) progression in HCC cells. Transwell assays were performed to determine migration and invasion of HCC cells. A lung metastasis mouse model was used to evaluated metastasis of HCC in vivo. The putative targets of miR-1296 were disclosed by public databases and a dual-luciferase reporter assay.

Results

We found that the expression of miR-1296 was reduced in HCC tissues and cell lines, and it was associated with metastasis and recurrence of HCC. Notably, miR-1296 overexpression inhibited migration, invasion and EMT progress of HCCLM3 cells, while miR-1296 loss facilitated these biological behaviors of Hep3B cells in vitro and in vivo. In addition, miR-1296 inversely regulated SRPK1 abundance by directly binding to its 3′-UTR, which subsequently resulted in suppression of p-AKT. Either SRPK1 re-expression or PI3K/AKT pathway activation, at least partially, abolished the effects of miR-1296 on migration, invasion and EMT progress of HCC cells. Furthermore, miR-1296 and SRPK1 expression were markedly correlated with adverse clinical features and poor prognosis of HCC patients. We showed that hypoxia was responsible for the underexpression of miR-1296 in HCC. And the promoting effects of hypoxia on metastasis and EMT of HCC cells were reversed by miR-1296.

Conclusions

Underexpression of miR-1296 potentially serves as a prognostic biomarker in HCC. Hypoxia-induced miR-1296 loss promotes metastasis and EMT of HCC cells probably by targeting SRPK1/AKT pathway.
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Metadata
Title
MicroRNA-1296 inhibits metastasis and epithelial-mesenchymal transition of hepatocellular carcinoma by targeting SRPK1-mediated PI3K/AKT pathway
Authors
Qiuran Xu
Xin Liu
Zhikui Liu
Zhenyu Zhou
Yufeng Wang
Jianfeng Tu
Lijie Li
Hangxing Bao
Liu Yang
Kangsheng Tu
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2017
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/s12943-017-0675-y

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