Open AccessmiR-186 Suppresses the Progression of Cholangiocarcinoma Cells Through Inhibition of Twist1
Author(s) -
Ming Zhang,
Baochang Shi,
Kai Zhang
Publication year - 2019
Publication title -
oncology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 57
eISSN - 1555-3906
pISSN - 0965-0407
DOI - 10.3727/096504019x15565325878380
Subject(s) - microrna , gene silencing , vimentin , cell growth , epithelial–mesenchymal transition , biology , cell culture , cancer research , downregulation and upregulation , cell migration , mmp9 , cell , cell cycle , microbiology and biotechnology , immunology , immunohistochemistry , gene , genetics
Deregulation of miR-186 and Twist1 has been identified to be involved in the progression of multiple cancers. However, the detailed molecular mechanisms underlying miR-186-involved cholangiocarcinoma (CCA) are still unknown. In this study, we found that miR-186 was downregulated in CCA tissues and cell lines, and negatively correlated with the expression of Twist1 protein. In vitro assays demonstrated that miR-186 mimics repressed cell proliferation, in vivo tumor formation, and caused cell cycle arrest. miR-186 mimics also inhibited the migration and invasion of CCLP1 and SG-231 cells. Mechanistically, the 3′-untranslated region (3′-UTR) of Twist1 mRNA is a direct target of miR-186. Further, miR-186 inhibited the expressions of Twist1, N-cadherin, vimentin, and matrix metallopeptidase 9 (MMP9) proteins, whereas it increased the expression of E-cadherin in CCLP1 and SG-231 cells. Silencing of Twist1 expression enhanced the inhibitory effects of miR-186 on the proliferation, migration, and invasion of CCLP1 and SG-231 cells. In conclusion, miR-186 inhibited cell proliferation, migration, invasion, and epithelial‐mesenchymal transition (EMT) through targeting Twist1 in human CCA. Thus, miR-186/Twist1 axis may benefit the development of therapies for CCA.