MiR-137 suppresses migration and invasion by targeting EZH2-STAT3 signaling in human hepatocellular carcinoma

Abstract

BackgroundHepatocellular carcinoma (HCC) is one of the most common and aggressive human malignancies and many cell-intrinsic identities and extrinsic epigenetic factors influence the metastatic potential of HCC cells. MicroRNA-137 is often found to be acting as tumor suppressors, however, how miR-137 involved in the metastasis progression in human HCC remains unclear. MethodQPCR was performed to detect the miR-137 mRNA levels in HCC cell linesand normal liver cell line HL7702.Then transwell assay and wound-healing assay were determined to investigate the motility of HCC cells introduced into lentivirus to ectopically upregulate endogenous miR-137 and EAH2 expressions. Targeting of enhancer of zeste homolog 2 (EZH2) gene by miR-137 in HCC was assessed by dual-luciferase activity assay and qPCR. Western blot was applied to explore the mechanism. In vivo, lung metastasis were evaluated using a mice tail vein injection model. ResultsIn this study, we found that miR-137 is decreased in HCC cell lines and had an inhibitory effect on HCC migration and invasion in vitro. EZH2 was a direct downstream target gene of miR-137 in HCC and miR-137 suppressed invasion and migration by targeting EZH2-STAT3 signaling in HCC cells. Furthermore, EZH2 overexpression reversed the miR-137 mimics-induced inhibitory effects on migration and invasion of HCC cells. In addition, miR-137 inhibited lung metastasis of HCC in vivo by targeting EZH2-STAT3 signaling. ConclusionMiR-137 suppressed migration and invasion by targeting EZH2-STAT3 signaling pathway in HCC cells in vitro and in vivo, suggesting miR-137-EZH2-STAT3 may be a potential therapeutic target for treatment of human hepatocellular carcinoma.