Knockdown of Circ_0081143 Mitigates Hypoxia-Induced Migration, Invasion, and EMT in Gastric Cancer Cells Through the miR-497-5p/EGFR Axis

Abstract

Background: Gastric cancer is one of the most common malignancies. Circular RNAs (circRNAs) are emerging as new players in the cancer paradigm. In the present study, the authors aimed to further explore the role and mechanism of circ_0081143 in GC progression under hypoxia. Materials and Methods: The expression levels of circ_0081143, miR-497-5p, and EGFR (epidermal growth factor receptor) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell migration and invasion abilities were determined by Transwell assay. The levels of vimentin, N-cadherin, E-cadherin, and EGFR were evaluated using Western blot. Dual-luciferase reporter assay was performed to confirm the targeted correlation between miR-497-5p and circ_0081143 or EGFR. Results: These data indicated that circ_0081143 expression was increased in GC tissues and cells. The knockdown of circ_0081143 relieved hypoxia-induced GC cell migration, invasion, and epithelial/mesenchymal transition (EMT). Moreover, circ_0081143 regulated the abundance of miR-497-5p through sponging miR-497-5p. The alleviative effects of circ_0081143 knockdown on GC cell migration, invasion, and EMT under hypoxia were mediated by miR-497-5p. Furthermore, miR-497-5p directly targeted EGFR, and miR-497-5p overexpression ameliorated hypoxia-induced GC cell migration, invasion, and EMT by downregulating EGFR. In addition, circ_0081143 modulated EGFR expression via acting as a competing endogenous RNA (ceRNA) of miR-497-5p in hypoxia-induced GC cells. Conclusion: The present work suggested that circ_0081143 knockdown ameliorated hypoxia-induced migration, invasion, and EMT in GC cells at least partly by the miR-497-5p/EGFR axis, illuminating a novel molecular target for GC treatment.

Keywords: EGFR; circ_0081143; gastric cancer (GC); hypoxia; miR-497-5p.