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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.
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Details
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
2 Department of Gastroenterology, Second Affiliated Hospital of Nanchang University, Nanchang, China
3 Department of Molecular Pharmacology, City of Hope Comprehensive Cancer Center and Beckman Research Institute, Duarte, CA, USA