Journal Article

MicroRNA-550a Acts as a Pro-Metastatic Gene and Directly Targets Cytoplasmic Polyadenylation Element-Binding Protein 4 in Hepatocellular Carcinoma

Ding, Jie, He, Xianghuo, Liang, Linhui, Ge, Chao, Tian, Qi, Huang, Shenglin, Li, Jinjun, Guo, Weijie, Zha, Ruopeng, Chen, Taoyang, Shi, Haibing, Wang, Qifeng

2012

Overview

MicroRNAs (miRNAs) are a class of small, non-coding RNA molecules that are often found at chromosomal breakpoints and play a vital role in human cancer. Our previous study found that miR-550a, a frequently amplified miRNA on 7p14.3, was upregulated in hepatocellular carcinoma (HCC). However, the possible functions and molecular mechanisms of miR-550a in HCC remain unknown. In this study, gain-of-function and loss-of-function assays revealed that miR-550a markedly promoted HCC cell migration and invasion. In addition, we discovered that cytoplasmic polyadenylation element binding protein 4 (CPEB4) was a potential target of miR-550a in HCC. Further analyses showed that knockdown of CPEB4 expression significantly facilitated HCC cell migration and invasion, which phenocopied the effects of miR-550a on HCC cells. Moreover, a decrease in CPEB4 expression mediated miR-550a-induced liver cancer cell migration and invasion. Interestingly, CPEB4 is frequently downregulated in HCC, and its expression levels correlate with the overall survival of HCC patients. Together, these results suggested that this newly identified miR-550a-CPEB4 axis may be involved in HCC cell metastasis. Moreover, the expression levels of CPEB4 could be used to predict outcomes in HCC patients. Our findings provide novel potential targets for HCC therapy and prognosis.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Analysis / Binding / Binding sites / Biology / Breakpoints / Cancer / Cancer genetics / Cancer metastasis / Cancer research / Carcinoma, Hepatocellular - genetics / Carcinoma, Hepatocellular - metabolism / Carcinoma, Hepatocellular - pathology / Cell adhesion & migration / Cell Line, Tumor / Cell migration / Cell Movement - genetics / Chromosomes / Cytoplasm - genetics / Cytoplasm - metabolism / Deoxyribonucleic acid / DNA / Down-Regulation / Esophagus / Gene expression / HEK293 Cells / Hep G2 Cells / Hepatocellular carcinoma / Hepatocytes / Humans / Hybridization / Laboratories / Liver / Liver cancer / Liver Neoplasms - genetics / Liver Neoplasms - metabolism / Liver Neoplasms - pathology / Lymphoma / Medical prognosis / Medicine / Mesothelioma / Metastases / MicroRNA / MicroRNAs / MicroRNAs - genetics / miRNA / Molecular modelling / Neoplasm Invasiveness / Neoplasm Metastasis / Non-coding RNA / Patients / Polyadenylation / Protein binding / Ribonucleic acid / RNA / RNA-Binding Proteins - genetics / RNA-Binding Proteins - metabolism / Tumors / Up-Regulation