miR-143-3p targeting of ITGA6 suppresses tumour growth and angiogenesis by downregulating PLGF expression via the PI3K/AKT pathway in gallbladder carcinoma

被引：107

作者：

Jin, Yun-Peng ^{[1
,2
,3
]}

Hu, Yun-Ping ^{[1
,2
,3
]}

Wu, Xiang-Song ^{[1
,2
,3
]}

Wu, Yao-Shi ^{[4
]}

Ye, Yuan-Yuan ^{[1
,2
,3
]}

Li, Huai-Feng ^{[1
,2
,3
]}

Liu, Yong-Chen ^{[1
,2
,3
]}

Jiang, Lin ^{[1
,2
,3
]}

Liu, Fa-Tao ^{[1
,2
,3
]}

Zhang, Yi-Jian ^{[1
,2
,3
]}

Hao, Ya-Juan ^{[1
,2
,3
]}

Liu, Xi-Yong ^{[5
,6
]}

Liu, Ying-Bin ^{[1
,2
,3
]}

机构：

[1] Shanghai Jiao Tong Univ, Dept Gen Surg, Xinhua Hosp, Sch Med, 1665 Kongjiang Rd, Shanghai 200092, Peoples R China

[2] Shanghai Jiao Tong Univ, Lab Gen Surg, Xinhua Hosp, Sch Med, 1665 Kongjiang Rd, Shanghai 200092, Peoples R China

[3] Shanghai Jiao Tong Univ, Inst Biliary Tract Dis, Sch Med, 1665 Kongjiang Rd, Shanghai 200092, Peoples R China

[4] Nanchang Univ, Dept Gastroenterol, Affiliated Hosp 2, Nanchang, Jiangxi, Peoples R China

[5] City Hope Comprehens Canc Ctr, Dept Mol Pharmacol, Duarte, CA 91010 USA

[6] Beckman Res Inst, Duarte, CA 91010 USA

来源：

CELL DEATH & DISEASE | 2018年 / 9卷

基金：

中国国家自然科学基金;

关键词：

CELL LUNG-CANCER; INTEGRIN ALPHA-6-BETA-4; PROLIFERATION; TRANSLATION; METASTASIS; PROTEIN;

D O I：

10.1038/s41419-017-0258-2

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

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 alpha 6 (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.

引用

页数：15

共 37 条

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MicroRNA-331-3p Promotes Proliferation and Metastasis of Hepatocellular Carcinoma by Targeting PH Domain and Leucine-Rich Repeat Protein Phosphatase [J].