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PLoS By Category | Recent PLoS Articles
Gastroenterology and Hepatology - Pathology - Surgery - Oncology - Molecular Biology

Ectopic Expression of MiR-125a Inhibits the Proliferation and Metastasis of Hepatocellular Carcinoma by Targeting MMP11 and VEGF
Published: Friday, June 29, 2012
Author: Qian Bi et al.

by Qian Bi, Shanhong Tang, Lin Xia, Rui Du, Rui Fan, Liucun Gao, Jiang Jin, Shuhui Liang, Zheng Chen, Guanghui Xu, Yongzhan Nie, Kaichun Wu, Jie Liu, Yongquan Shi, Jie Ding, Daiming Fan

Background

Studies have been shown that miR-125a plays an important role in carcinogenesis, however, the role of miR-125a in hepatocellular carcinoma (HCC) remains elusive.

Methodology/Principal

Real time-PCR (qRT-PCR) was performed to test the significance of miR-125a in HCC. Ectopic expression of miR-125a was used to test the influences of miR-125a on proliferation and metastasis of HCC cells in vitro and in vivo. Predicted target genes of miR-125a were determined by dual-luciferase reporting, qRT-PCR, and western blot (WB) analyses. Then immunohistochemical staining (IHC) was used to detect the expression of target genes, and the correlations and prognostic values of miR-125a and its target genes were also investigated.

Conclusions/Significance

Decreased miR-125a was observed in both HCC tissues and cell lines, and associated with patients’ aggressive pathologic features. Up-regulating miR-125a significantly inhibited the malignant phenotypes by repressing the expression of matrix metalloproteinase 11 (MMP11) and vascular endothelial growth factor A (VEGF-A) both in vitro and in vivo. Furthermore, miR-125a expression was inversely correlated with both MMP11 and VEGF-A expression in HCC tissues. Inhibiting miR-125a could increase both MMP11 and VEGF-A expression, and RNA interference targeting MMP11 or VEGF-A mRNA could rescue the loss of miR-125a functions. MiR-125a inhibits the proliferation and metastasis of HCC by targeting MMP11 and VEGF-A. Up-regulation of miR-125a might be a promising approach and a prognostic marker for HCC.

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