miR-142-3p Inhibits the Metastasis of Hepatocellular Carcinoma Cells by Regulating HMGB1 Gene Expression

Abstract

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.

Objective: The aim was to investigate the role of miR-142-3p on HMGB1 expression in hepatocellular carcinoma.

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.

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.

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.

Keywords: HMGB1; Hepatocellular carcinoma; invasion; miR-142-3p; migration; tumor suppressor..