MiR-122 inhibits epithelial-mesenchymal transition in hepatocellular carcinoma by targeting Snail1 and Snail2 and suppressing WNT/β-cadherin signaling pathway
- Departement of Hepatobiliary Surgery, The First People's Hospital of Yunnan Province, Kunming 650030, Yunnan (China)
- Departement of Hepatobiliary Surgery, Kunming General Hospital, PLA, Kunming 650032, Yunnan (China)
The downregulation of microRNA-122 (miR-122) had been reported to be associated with tumor invasion and metastasis in hepatocellular carcinoma (HCC). However, the underlying mechanisms of miR-122 involved in epithelial-mesenchymal transition (EMT) still need to be investigated. In the study, we demonstrated that miR-122 was significantly downregulated in HCC tissues compared with adjacent normal tissues. MiR-122 expression was closely correlated with tumor size, vascular invasion and American Joint Committee on Cancer (AJCC) stage of HCC patients. Kaplan-Meier survival curve and log rank test demonstrated that lower miR-122 predicted poor Disease-free survival (DFS) and overall survival (OS) time in patients. Univariate and multivariate Cox analysis confirmed that tumor size, vascular invasion, American Joint Committee on Cancer (AJCC) stage and lower miR-122 expression levels were independent risk factors for DFS or OS in HCC patients. Function assays demonstrated that upregulation of miR-122 inhibited the cell proliferation, colony formation and cell invasion in HCC cells, however, downregulation of miR-122 promoted cell proliferation, colony formation and cell invasion in HCC cells. Moreover, we demonstrated that increased miR-122 expression levels in HCC cells inhibited epithelial-mesenchymal transition (EMT) by suppressing the expression of ZEB1/2, Snail1/2, N-cadherin, Vimentin and upregulating the E-cadherin expression. However, downregulation of miR-122 caused an opposite effects. Mechanisms study found that miR-122 overexpression inhibited the EMT process by targeting Snail1 and Snail2 and regulated their expression levels in HCC cells. In addition, we also revealed that upregulated miR-122 expression suppressed the Wnt/β-catenin signaling pathway. Taken together, our results indicated that miR-122 may be a biomarker for predicting prognosis of HCC and therapeutic target for HCC patients. - Graphical abstract: MiR-122 inhibits epithelial-mesenchymal transition in hepatocellular carcinoma by targeting Snail1 and Snail2 and suppressing WNT/β-cadherin signaling pathway. - Highlights: • MiR-122 expression is significantly downregulated in HCC and associated poor prognosis of patients. • MiR-122 inhibits HCC cell proliferation, invasion and EMT process by targeting Snail1 and Snail2. • miR-122 suppresses the Wnt/β-catenin signaling pathway.
- OSTI ID:
- 22738182
- Journal Information:
- Experimental Cell Research, Vol. 360, Issue 2; Other Information: Copyright (c) 2017 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0014-4827
- Country of Publication:
- United States
- Language:
- English
Similar Records
miR-612 suppresses the stemness of liver cancer via Wnt/β-catenin signaling
3,5,4′-Trimethoxystilbene, a natural methoxylated analog of resveratrol, inhibits breast cancer cell invasiveness by downregulation of PI3K/Akt and Wnt/β-catenin signaling cascades and reversal of epithelial–mesenchymal transition