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  • miR-1301 inhibits hepatocellular carcinoma cell migration, invasion, and angiogenesis by decreasing Wnt/β-catenin signaling through targeting BCL9.

miR-1301 inhibits hepatocellular carcinoma cell migration, invasion, and angiogenesis by decreasing Wnt/β-catenin signaling through targeting BCL9.

Cell death & disease (2017-08-18)
Chao Yang, Yonghua Xu, Feng Cheng, Yuanchang Hu, Shikun Yang, Jianhua Rao, Xuehao Wang
RESUMO

Metastasis is the major cause of the poor prognosis of hepatocellular carcinoma (HCC), and increasing evidence supports the contribution of miRNAs to cancer progression. However, the exact relationship between the level of miR-1301 expression and HCC cell migration, invasion, and angiogenesis remains largely unknown. Quantitative PCR was used to evaluate the level of miR-1301 expression in HCC tissues and cell lines. Transwell and tube-formation assays were used to measure the effects of miR-1301 on HCC cell migration and invasion, and angiogenesis, respectively. Luciferase reporter assays and western blotting were used to confirm the miR-1301 target genes. We found that miR-1301 was significantly downregulated in HCC tissues and cell lines. Low miR-1301 expression was associated with tumor vascular invasion and Edmondson grade. Gain- and loss-of-function assays demonstrated that miR-1301 inhibited the migration, invasion, epithelial-mesenchymal transition, and angiogenesis of HCC cells in vitro and in vivo. BCL9, upregulated in HCC tissues compared with matched adjacent normal tissues, was inversely correlated to miR-1301 levels in HCC tissues. Through reporter gene and western blot assays, BCL9 was shown to be a direct miR-1301 target. BCL9 overexpression could partially reverse the effects of miR-1301 on HCC cell migration and invasion. Most importantly, miR-1301 overexpression markedly suppressed the death of xenograft mouse models of cancer by reducing tumor load, metastasis, and host angiogenesis by downregulating BCL9, β-catenin, and vascular endothelial growth factor expression in tumor cells. Our observations suggested that miR-1301 inhibits HCC migration, invasion, and angiogenesis via decreasing Wnt/β-catenin signaling through targeting BCL9, and might be a therapeutic target for HCC.

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MISSION® esiRNA, targeting human BCL9