MicroRNA-194 inhibits cell invasion and migration in hepatocellular carcinoma through PRC1-mediated inhibition of Wnt/β-catenin signaling pathway

Abstract

Background: Hepatocellular carcinoma (HCC) is a commonly occurring malignancy accompanied by significant mortality rates. More recently, extensive investigations into microRNA (miRNA) expression profiles have been conducted to identify their ability to inhibit tumors. Thus, this study explored the role of miR-194 in epithelial-mesenchymal transition (EMT), cell invasion and migration through Wnt/β-catenin signaling pathway by binding to protein regulator of cytokinesis 1 (PRC1) in HCC.

Methods: Initially, HCC related microarray data were retrieved and analyzed, and regulatory miRNAs of PRC1 were predicted accordingly. Next, the roles of miR-194, PRC1, and Wnt/β-catenin signaling pathway in HCC were determined, with relationship between PRC1 and miR-194 being verified subsequently. The role of miR-194 in cell EMT, migration, proliferation and invasion was evaluated through gain- and loss- function studies. Finally, tumor xenograft in nude mice was induced to assess tumor growth of HCC.

Results: miR-194 affected HCC development in Wnt/β-catenin signaling pathway with putative binding sites to PRC1. MiR-194 could target PRC1. MiR-194 was downregulated while PRC1 was upregulated in HCC tissues. Additionally, miR-194 elevation and PRC1 silencing could suppress EMT, growth, proliferation, invasion, and migration in HCC cells by inactivating Wnt/β-catenin signaling pathway.

Conclusion: Taken together, this study demonstrated that miR-194 inhibited EMT, cell invasion and migration through inactivation of PRC1-dependent Wnt/β-catenin signaling pathway.

Keywords: Epithelial-mesenchymal transition; Hepatocellular carcinoma; Invasion; MicroRNA-194; Migration; Protein regulator of cytokinesis 1; Wnt/β-catenin signaling pathway.