Open AccessmiR-143-3p targeting of ITGA6 suppresses tumour growth and angiogenesis by downregulating PLGF expression via the PI3K/AKT pathway in gallbladder carcinoma
Author(s) -
Yunpeng Jin,
Yunping Hu,
Xiangsong Wu,
Yaoshi Wu,
Yuanyuan Ye,
Huai-Feng Li,
Yongchen Liu,
Lin Jiang,
Fa-tao Liu,
Yi-Jian Zhang,
Yajuan Hao,
Xiyong Liu,
Yingbin Liu
Publication year - 2018
Publication title -
cell death and disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.482
H-Index - 111
ISSN - 2041-4889
DOI - 10.1038/s41419-017-0258-2
Subject(s) - angiogenesis , cancer research , protein kinase b , pi3k/akt/mtor pathway , gallbladder cancer , medicine , western blot , microrna , in vivo , cancer , biology , signal transduction , microbiology and biotechnology , biochemistry , gene
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.