Journal Article

Over-Expression of miR-106b Promotes Cell Migration and Metastasis in Hepatocellular Carcinoma by Activating Epithelial-Mesenchymal Transition Process

Yau, Wing Lung, Chow, Ariel Ka Man, Chan, Sylvia Tsz Ching, Ng, Lui, Man, Kwan, Chan, Jacky Yu Ki, Wo, Jana Yim Hung, Pang, Roberta Wen Chi, Ng, Kevin Tak Pan, Poon, Ronnie Tung Ping, Lam, Colin Siu Chi

2013

Overview

Hepatocellular carcinoma (HCC) is one the the most fatal cancers worldwide. The poor prognosis of HCC is mainly due to the developement of distance metastasis. To investigate the mechanism of metastasis in HCC, an orthotopic HCC metastasis animal model was established. Two sets of primary liver tumor cell lines and corresponding lung metastasis cell lines were generated. In vitro functional analysis demonstrated that the metastatic cell line had higher invasion and migration ability when compared with the primary liver tumor cell line. These cell lines were subjected to microRNA (miRNAs) microarray analysis to identify differentially expressed miRNAs which were associated with the developement of metastasis in vivo. Fifteen human miRNAs, including miR-106b, were differentially expressed in 2 metastatic cell lines compared with the primary tumor cell lines. The clinical significance of miR-106b in 99 HCC clinical samples was studied. The results demonstrated that miR-106b was over-expressed in HCC tumor tissue compared with adjacent non-tumor tissue (p = 0.0005), and overexpression of miR-106b was signficantly correlated with higher tumor grade (p = 0.018). Further functional studies demonstrated that miR-106b could promote cell migration and stress fiber formation by over-expressing RhoGTPases, RhoA and RhoC. In vivo functional studies also showed that over-expression of miR-106b promoted HCC metastasis. These effects were related to the activation of the epithelial-mesenchymal transition (EMT) process. Our results suggested that miR-106b expression contributed to HCC metastasis by activating the EMT process promoting cell migration in vitro and metastasis in vivo.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Animal models / Animals / Biomarkers, Tumor - metabolism / Biotechnology / Cancer metastasis / Cancer therapies / Carcinoma, Hepatocellular - genetics / Carcinoma, Hepatocellular - pathology / Cell cycle / Cell Line, Tumor / Cell migration / Cell Movement - genetics / Comparative analysis / Cytoskeleton - metabolism / Disease Models, Animal / DNA microarrays / Epithelial-Mesenchymal Transition - genetics / Female / Functional analysis / Gene expression / Gene Expression Regulation, Neoplastic / Gene Knockdown Techniques / Growth factors / Hepatitis / Hepatocellular carcinoma / Hepatocytes / Humans / In vivo methods and tests / Infections / Liver / Liver cancer / Liver Neoplasms - genetics / Liver Neoplasms - pathology / Lung Neoplasms - genetics / Lung Neoplasms - secondary / Lungs / Male / Medical research / Medicine / Mesenchyme / Metastases / Metastasis / Mice / Mice, SCID / MicroRNA / MicroRNAs / MicroRNAs - genetics / MicroRNAs - metabolism / Middle Aged / miRNA / Neoplasm Invasiveness / Neoplasm Metastasis / Oligonucleotide Array Sequence Analysis / Overexpression / Prognosis / Prostate / Rapid prototyping / rho GTP-Binding Proteins - metabolism / RhoA protein / Ribonucleic acid / RNA / Stem cells / Studies / Surgery / Tumor cell lines / Tumors / Up-Regulation - genetics