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

Abstract

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.Electronic supplementary materialThe online version of this article (10.1186/s12885-017-3875-3) contains supplementary material, which is available to authorized users.

EphA2‐to‐YAP pathway drives gastric cancer growth and therapy resistance

“…27 YAP phosphorylation by tyrosine kinase c-Abl is a critical step in selective activation of proapoptotic genes in response to DNA damage. 8,11,12 In present study, we further confirm the role of EphA2 in GC growth and development, and find that the regulation of YAP by EphA2 is one of the major mechanisms underlying EphA2-driven GC development, progression and therapy resistance. The Eph receptor tyrosine kinases and their ligands called ephrins play important roles in various physiological and disease processes.…”

“…31 We and others have previously reported that EphA2 overexpression is associated with poor prognosis for GC patients and promotes the EMT and invasion of GC cells through the Wnt/β-catenin pathway. 8,11,12 In present study, we further confirm the role of EphA2 in GC growth and development, and find that the regulation of YAP by EphA2 is one of the major mechanisms underlying EphA2-driven GC development, progression and therapy resistance.…”

“…[3][4][5] EphA2 is a key member of the erythropoietin-producing hepatocellular (Eph) receptors, which is the largest subfamily of receptor tyrosine kinases (RTKs). 8,11,12 However, the exact mechanisms underlying the role of EphA2 in GC development, progression and therapyresistance is unclear. 10 We and others have reported that EphA2 overexpression is associated with poor prognosis for gastric cancer patients and promotes the epithelial-mesenchymal transition (EMT) through the Wnt/β-catenin pathway in gastric cancer cells.…”

“…10 We and others have reported that EphA2 overexpression is associated with poor prognosis for gastric cancer patients and promotes the epithelial-mesenchymal transition (EMT) through the Wnt/β-catenin pathway in gastric cancer cells. 8,11,12 However, the exact mechanisms underlying the role of EphA2 in GC development, progression and therapyresistance is unclear.…”

MicroRNA‑495 targets Notch1 to prohibit cell proliferation and invasion in oral squamous cell carcinoma

“…At present, 2,588 mature human miRNAs have been detected in the human genome and are estimated to modulate the expression of >30% of all the protein-coding genes (11). Previously, miRNAs have been reported to be abnormally expressed in almost all types of human cancers (12)(13)(14). In addition, studies have indicated that numerous miRNAs are dysregulated in OSCC, including miRNA (miR)-433 (15), miR-195-5p (16), miR-27b (17) and miR-373-3p (18).…”