miR-302b inhibits tumorigenesis by targeting EphA2 via Wnt/ β-catenin/EMT signaling cascade in gastric cancer
Jin Huang,
Yijing He,
Howard L. Mcleod,
Yanchun Xie,
Desheng Xiao,
Huabin Hu,
Pan Chen,
Liangfang Shen,
Shan Zeng,
Xianli Yin,
Jie Ge,
Li Li,
Lanhua Tang,
Jian Ma,
Zihua Chen
Affiliations
Jin Huang
Department of Oncology, Xiangya Hospital, Central South University
Yijing He
Department of Dermatology, XiangYa Hospital, Central South University
Howard L. Mcleod
Department of Clinical Pharmacology, XiangYa Hospital, Central South University
Yanchun Xie
Department of Oncology, Xiangya Hospital, Central South University
Desheng Xiao
Department of Pathology, Xiangya Hospital, Central South University
Huabin Hu
The Sixth Affiliated Hospital of Sun Yat-Sen University
Pan Chen
Department of Hepatobiliary Surgery, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University
Liangfang Shen
Department of Oncology, Xiangya Hospital, Central South University
Shan Zeng
Department of Oncology, Xiangya Hospital, Central South University
Xianli Yin
Department of gastroenterology and urology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University
Jie Ge
Department of General Surgery, Xiangya Hospital of Central South University
Li Li
Department of Oncology, Xiangya Hospital, Central South University
Lanhua Tang
Department of Oncology, Xiangya Hospital, Central South University
Jian Ma
Cancer Research Institute, Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Central South University
Zihua Chen
Department of General Surgery, Xiangya Hospital of Central South University
Abstract Background EphA2 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. Methods We 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. Results Our 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. Conclusions miR-302b serves as a critical suppressor of GC cell tumorigenesis and metastasis by targeting the EphA2/Wnt/β-catenin/EMT pathway.
