miR-302b inhibits tumorigenesis by targeting EphA2 via Wnt/ β-catenin/EMT signaling cascade in gastric cancer

BMC Cancer

Research Article

Jian Ma¹  Howard L. Mcleod²  Yijing He³  Jie Ge⁴  Zihua Chen⁴  Pan Chen⁵  Shan Zeng⁶  Lanhua Tang⁶  Jin Huang⁶  Li Li⁶  Liangfang Shen⁶  Yanchun Xie⁶  Desheng Xiao⁷  Xianli Yin⁸  Huabin Hu⁹ 

[1] Cancer Research Institute, Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Central South University, No.138 Tongzipo Road, Changsha, China;Department of Clinical Pharmacology, XiangYa Hospital, Central South University, 410008, Changsha, China;Hunan Key Laboratory of Pharmacogenetics, 410008, Changsha, China;Moffitt Cancer Center, DeBartolo Family Personalized Medicine Institute, 33612, Tampa, FL, USA;Department of Dermatology, XiangYa Hospital, Central South University, 410008, Changsha, China;Department of General Surgery, Xiangya Hospital of Central South University, No.87 Xiangya Road, 410008, Changsha, People’s Republic of China;Department of Hepatobiliary Surgery, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, 410013, Changsha, China;Department of Oncology, Xiangya Hospital, Central South University, 410008, Changsha, China;Department of Pathology, Xiangya Hospital, Central South University, 410008, Changsha, China;Department of gastroenterology and urology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, 410013, Changsha, China;The Sixth Affiliated Hospital of Sun Yat-Sen University, 510655, Guangzhou, China;

关键词: miR-302b;    EphA2;    Gastric cancer;    Epithelial-mesenchymal transition;    Wnt/β-catenin;   

DOI  :  10.1186/s12885-017-3875-3

 received in 2017-05-03, accepted in 2017-12-04,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundEphA2 is a crucial oncogene in gastric cancer (GC) development and metastasis, this study aims to identify microRNAs that target it and serve as key regulators of gastric carcinogenesis.MethodsWe identified several potential microRNAs targeting EphA2 by bioinformatics websites and then analyzed the role of miR-302b in modulating EphA2 in vitro and in vivo of GC, and it’s mechanism.ResultsOur analysis identified miR-302b, a novel regulator of EphA2, as one of the most significantly downregulated microRNA (miRNA) in GC tissues. Overexpression of miR-302b impaired GC cell migratory and invasive properties robustly and suppressed cell proliferation by arresting cells at G0–G1 phase in vitro. miR-302b exhibited anti-tumor activity by reversing EphA2 regulation, which relayed a signaling transduction cascade that attenuated the functions of N-cadherin, β-catenin, and Snail (markers of Wnt/β-catenin and epithelial-mesenchymal transition, EMT). This modulation of EphA2 also had distinct effects on cell proliferation and migration in GC in vivo.ConclusionsmiR-302b serves as a critical suppressor of GC cell tumorigenesis and metastasis by targeting the EphA2/Wnt/β-catenin/EMT pathway.

【 授权许可】

CC BY   
© The Author(s). 2017