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

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.

• Authors: 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
• Journal: BMC cancer (BMC Cancer) Vol. 17 Issue 1 Pg. 886 (12 22 2017) ISSN: 1471-2407 [Electronic] England
• PMID: 29273006 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CTNNB1 protein, human
• MIRN302A microRNA, human
• MicroRNAs
• Wnt Proteins
• beta Catenin
• Receptor, EphA2

Topics

• Animals
• Apoptosis
• Carcinogenesis (genetics, metabolism, pathology)
• Cell Cycle
• Cell Movement
• Cell Proliferation
• Epithelial-Mesenchymal Transition
• Gene Expression Regulation, Neoplastic
• Humans
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• MicroRNAs (genetics)
• Receptor, EphA2 (genetics, metabolism)
• Stomach Neoplasms (genetics, metabolism, pathology)
• Tumor Cells, Cultured
• Wnt Proteins (genetics, metabolism)
• Xenograft Model Antitumor Assays
• beta Catenin (genetics, metabolism)