microRNA-34a inhibits epithelial mesenchymal transition in human cholangiocarcinoma by targeting Smad4 through transforming growth factor-beta/Smad pathway

BMC Cancer

Research Article

Guodong Li¹  Wen Bi²  Lianmeng Yang²  Dequan Wu²  Lei Yao²  Pengfei Qiao² 

[1] Department of General Surgery, the Fourth Affiliated Hospital of Harbin Medical University, 150001, Harbin, People's Republic of China;Bio-Bank of Department of General Surgery, the Fourth Affiliated Hospital of Harbin Medical University, 150001, Harbin, People's Republic of China;Department of General Surgery, the Second Affiliated Hospital of Harbin Medical University, 150086, Harbin, People's Republic of China;

关键词: Cholangiocarcinoma;    miR-34a;    Smad4;    Epithelial-mesenchymal transition;    Transforming growth factor-beta;   

DOI  :  10.1186/s12885-015-1359-x

 received in 2014-11-04, accepted in 2015-04-23,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundExtrahepatic Cholangiocarcinoma (EHCC) is one of the uncommon malignancies in the digestive system which is characterized by a poor prognosis. Aberrations of miRNAs have been shown involved in the progression of this disease. In this study, we evaluated the expression and effects of miR-34a on EHCC.MethodsmiR-34a expression levels were detected in EHCC tissues, adjacent non-tumor tissues, normal bile duct (NBD) specimens of patients and cholangiocarcinoma (CC) cell lines by quantitative real-time polymerase chain reaction (qRT-PCR). Relationships between miR-34a with clinical characteristics of EHCC patients were further analyzed. Computational search, functional luciferase assay and western blot were further used to demonstrate the downstream target of miR-34a in CC cells. Immunohistochemistry was carried on to identify the downstream target gene of miR-34a in EHCC patients. Cell morphology, invasion and migration assays were further applied to confirm the anti-carcinogenic effects of miR-34a through the downstream target.ResultsmiR-34a expression was significantly decreased in human EHCC tissues and CC cell lines when compared with the adjacent non-tumor tissues and normal bile duct tissues. miR-34a was found correlated with the migration and invasion in EHCC patients. Smad4 was over-expressed in most of the EHCC patients and was further demonstrated as one of the downstream targets of miR-34a, which was involved in the progression of EHCC. Moreover, activation of miR-34a suppressed invasion and migration through TGF-beta/Smad4 signaling pathway by epithelial-mesenchymal transition (EMT) in vitro.ConclusionsTaken together, our results suggest that miR-34a inhibits invasion and migration by targeting Smad4 to suppress EMT through TGF- beta/Smad signaling pathway in human EHCC.

【 授权许可】

Unknown   
© Qiao et al. 2015. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.