Abstract

Gallbladder cancer (GBC) is the most common malignant tumour of the biliary track system. Angiogenesis plays a pivotal role in the development and progression of malignant tumours. miR-143-3p acts as a tumour suppressor in various cancers. Their role in GBC is however less well defined. Here we show that the expression levels of miR-143-3p were decreased in human GBC tissues compared with the non-tumour adjacent tissue (NAT) counterparts and were closely associated with overall survival. We discovered that miR-143-3p was a novel inhibitor of tumour growth and angiogenesis in vivo and in vitro. Our antibody array, ELISA and PLGF rescue analyses indicated that PLGF played an essential role in the antiangiogenic effect of miR-143-3p. Furthermore, we used miRNA target-prediction software and dual-luciferase assays to confirm that integrin α6 (ITGA6) acted as a direct target of miR-143-3p. Our ELISA and western blot analyses confirmed that the expression of PLGF was decreased via the ITGA6/PI3K/AKT pathway. In conclusion, miR-143-3p suppresses tumour angiogenesis and growth of GBC through the ITGA6/PI3K/AKT/PLGF pathways and may be a novel molecular therapeutic target for GBC.

Details

Title
miR-143-3p targeting of ITGA6 suppresses tumour growth and angiogenesis by downregulating PLGF expression via the PI3K/AKT pathway in gallbladder carcinoma
Author
Yun-Peng, Jin 1 ; Yun-Ping, Hu 1 ; Xiang-Song, Wu 1 ; Yao-Shi, Wu 2 ; Yuan-Yuan, Ye 1 ; Huai-Feng Li 1 ; Yong-Chen, Liu 1 ; Jiang, Lin 1 ; Fa-Tao Liu 1 ; Yi-Jian, Zhang 1 ; Ya-Juan, Hao 1 ; Xi-Yong, Liu 3 ; Ying-Bin, Liu 1 

 Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Institute of Biliary Tract Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China 
 Department of Gastroenterology, Second Affiliated Hospital of Nanchang University, Nanchang, China 
 Department of Molecular Pharmacology, City of Hope Comprehensive Cancer Center and Beckman Research Institute, Duarte, CA, USA 
Pages
1-15
Publication year
2018
Publication date
Feb 2018
Publisher
Springer Nature B.V.
e-ISSN
20414889
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2019449626
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.