Y. Fu, L.-Q. Sun, Y. Huang, J. Quan, X. Hu, D. Tang, R. Kang, N. Li* and X.-G. Fan* Pages 135 - 141 ( 7 )
Background: Non-coding small RNAs are involved in organism development, and their aberrant regulation induces various diseases, including hepatocellular carcinoma (HCC), but their exact mechanisms have not been determined. </P><P> Objective: The aim was to investigate the role of miR-142-3p on HMGB1 expression in hepatocellular carcinoma. </P><P> Methods: Expression levels of miR-142-3p in HCC tissues and cultured cells were measured by RT-PCR. The invasion and metastasis abilities of HepG2 cells according to Transwell migration and invasion assays, and protein expression was measured by western blotting. </P><P> Results: The present study reported that miR-142-3p promotes the invasion and migration of HCC cells. miR-142-3p levels are lower in HCC tissues than in adjacent non-cancerous tissues, suggesting a tumor suppressor role for miR-142-3p. Highmobility group box protein 1 (HMGB1) is an oncogene that promotes the metastasis of HCC. miR-142-3p or HMGB1 knockdown alone inhibits the invasion and migration of HCC cells, and HMGB1 overexpression impedes the effect of miR-142-3p. Further studies showed that HMGB1 is a direct target gene of miR-142-3p in HCC. miR-142-3p represses HMGB1 gene transcription by directly binding to the 3′ untranslated region (UTR) of HMGB1, thereby inhibiting cancer cell invasion and migration. </P><P> Conclusion: This study, for the first time, reports that miR-142-3p is a novel tumor suppressor that inhibits the invasion and migration of HCC cells by directly regulating gene transcription of HMGB1. Thus, miR-142-3p may be a potential diagnostic and therapeutic biomarker for HCC patients.
Hepatocellular carcinoma, miR-142-3p, HMGB1, migration, invasion, tumor suppressor.
Department of Infectious Diseases and Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha 410008, Center for Molecular Medicine, Xiangya Hospital; Collaborative Innovation Center for Cancer Medicine, Central South University, Changsha 410078, Department of Infectious Diseases and Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha 410008, Department of Infectious Diseases and Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha 410008, Department of Infectious Diseases and Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha 410008, Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213, Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213, Department of Blood Transfusion, Xiangya Hospital, Central South University, Changsha 410008, Department of Infectious Diseases and Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha 410008