Bin Huang1, Manping Huang1, Qin Li2. 1. Department of Intervention, Hunan Provincial Cancer Hospital, Changsha 410009, PR China. 2. Department of Gynecology, Affiliated Hospital of Hunan Institute of Traditional Chinese Medicine, Changsha 410009, PR China. Electronic address: liqinlq2017123112@163.com.
Abstract
BACKGROUND: Hepatocellular 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. METHOD: QPCR 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. RESULTS: In 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. CONCLUSION: MiR-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.
BACKGROUND:Hepatocellular carcinoma (HCC) is one of the most common and aggressive humanmalignancies 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. METHOD: QPCR 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. RESULTS: In 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. CONCLUSION:MiR-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 humanhepatocellular carcinoma.
Authors: Rania H Mahmoud; Enas Mamdouh Hefzy; Olfat G Shaker; Tarek I Ahmed; Noha K Abdelghaffar; Essam A Hassan; Amal A Ibrahim; Doaa Y Ali; Mohamed M Mohamed; Omayma O Abdelaleem Journal: Sci Rep Date: 2021-10-08 Impact factor: 4.379