circ_0023642 promotes malignant biological behaviors of gastric cancer cells via regulating miR-508-3p/ERBB4 axis / 中国肿瘤生物治疗杂志

ABSTRACT

@#Objective: To explore the influence of circ_0023642 on the proliferation and metastasis of gastric cancer GMC-803 cells by modulating miR-508-3p/ERBB4 axis. Methods: Cancer tissues and corresponding para-cancer normal tissues from 31 gastric cancer patients, who underwent surgical resection at the Second People's Hospital of Nantong City from May 2015 to March 2018, were collected for this study; meanwhile, gastric cancer cell lines (MGC-803, MKN-45 and MKN-28) were also collected. qPCR was performed to determine the expression levels of circ_0023642 and miR-508-3p in above mentioned tissues and cell lines. WB was applied to measure the expressions of ERBB4, E-cadherin, N-cadherin and Vimentin in MGC-803 cells. CCK-8 assay and Transwell assay were used to evaluate the effects of circ_0023462 and miR-508-3p expression on proliferation, migration and invasion of MGC-803 cells. Dual-luciferase reporter gene was carried out to validate whether miR-508-3p could bind to the 3' UTR of circ_0023642 and ERBB4. Results: Compared with para-cancer tissues or normal gastric mucosal cells, the expression of circ_0023642 was significantly up-regulated in gastric cancer tissues and cells lines, and the expression was highest in MGC-803 cells (P<0.05 or P<0.01). Silencing circ_0023642 dramatically decreased the proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) of MGC-803 cells (P<0.05 or P<0.01). Both circ_0023642 and ERBB4 could target the binding sites of miR-508-3p. Further experiments confirmed that circ_ 0023642 promoted the proliferation, migration, invasion and EMT of MGC-803 cells by sponging miR-508-3p (P<0.05 or P<0.01). Conclusion: circ_0023642, by competing ERBB4 to bind with miR-508-3p, promotes the proliferation and metastasis of gastric cancer MGC-803 cells, thus could be used as a marker for the clinical diagnosis of gastric cancer.