Deregulation of microRNA expression occurs early and accumulates in early stages of HBV-associated multistep hepatocarcinogenesis

Abstract

Background & Aims: Deregulation of microRNAs (miRNAs) plays an important role in human carcinogenesis. However, miRNA deregulation in the pre-malignant lesions and expression changes during multistep hepatocarcinogenesis remain elusive. Methods: In this study, we investigated the expression changes of seven cancer-related miRNAs during the early stages of HBV related hepatocarcinogenesis. miRNA was extracted from formalin fixed paraffin embedded (FFPE) dysplastic nodules (DN), small HCCs, and their corresponding non-tumorous livers. Expression changes of miRNAs were examined by real-time RT-qPCR. Results: We found that down-regulation of miR-145 and miR-199b and up-regulation of miR-224 were frequently observed in pre-malignant DNs and these changes persisted throughout HCC development. Restoration of miR-145 in both HepG2 and Hep3B HCC cells significantly inhibited cell proliferation and reduced cell migration and cell invasion. Furthermore, these inhibitory functions of miR-145 could be substantially reduced by an anti-miR-145 inhibitor. Conclusions: Our results showed that miRNA deregulation was an early event and accumulated throughout the various steps of HBV-associated hepatocarcinogenesis. Our findings also suggest that miR-145 is a candidate tumor suppressive miRNA and may play an important role in HCC development. © 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.