Ectopic expression of MiR-125a inhibits the proliferation and metastasis of hepatocellular carcinoma by targeting MMP11 and VEGF

• Published in: PloS one 2012-06, Vol.7 (6), p.e40169
• Main Authors: Bi, Qian, Tang, Shanhong, Xia, Lin, Du, Rui, Fan, Rui, Gao, Liucun, Jin, Jiang, Liang, Shuhui, Chen, Zheng, Xu, Guanghui, Nie, Yongzhan, Wu, Kaichun, Liu, Jie, Shi, Yongquan, Ding, Jie, Fan, Daiming
• Format: Article
• Language: English
• Subjects: Aged; Analysis; Animals; Biology; Cancer metastasis; Carcinogenesis; Carcinogens; Carcinoma, Hepatocellular - enzymology; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - pathology; Cell Line, Tumor; Cell Proliferation; Development and progression; Down-Regulation - genetics; Ectopic expression; Female; Gene expression; Gene Expression Regulation, Neoplastic; Genes; Hepatocellular carcinoma; Humans; Immunohistochemistry; In vivo methods and tests; Kaplan-Meier Estimate; Liver cancer; Liver Neoplasms - enzymology; Liver Neoplasms - genetics; Liver Neoplasms - pathology; Male; Matrix metalloproteinase; Matrix Metalloproteinase 11 - genetics; Matrix Metalloproteinase 11 - metabolism; Medical prognosis; Medicine; Metalloproteinase; Metastases; Mice; MicroRNAs - genetics; MicroRNAs - metabolism; Middle Aged; mRNA; Multivariate Analysis; Neoplasm Invasiveness; Neoplasm Metastasis; Prognosis; Ribonucleic acid; RNA; RNA-mediated interference; Rodents; Studies; Target detection; Tissues; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - genetics; Vascular Endothelial Growth Factor A - metabolism
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0040169

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. 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. 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.