miR-93 activates ERK pathway to promote proliferation and migration of NSCLC cells via targeting EphA4 / 中国肿瘤生物治疗杂志

ABSTRACT

@#[Abstract] Objective: To investigate the effect of miR-93/EphA4 (Eph receptor A4) axis on the proliferation and migration of nonsmall cell lung cancer (NSCLC) H460 and H1299 cells via regulating extracellular regulated protein kinases (ERK) pathway. Methods: The expression levels of miR-93 in H460 and H1299 cells was detected by qPCR. miR-93 mimics and EphA4 overexpression plasmids were transfected into H460 cells and miR-93 inhibitor was transfected into H1299 cells respectively, after which MTT assay and Transwell assay were used to detect the effects of miR-93 on proliferation and migration of transfected cells. The targeted regulatory relationship betweenmiR-93andEphA4wasverifiedbyDual-luciferasereportergeneassay.Theexpression levels of PCNA(proliferating cell nuclear antigen), EphA4, ERK and p-ERK were detected by Westernblotting.The effects of simultaneous overexpression of miR-93 and EphA4 on proliferation and migration of H460 cells were detected by MTT assay and Transwell assay. Results: The expression of miR-93 in H1299 cells was higher than that in H460 cells (P<0.01). Overexpression of miR-93 promoted proliferation and migration of H460 cells (all P<0.01), and knockdown of miR-93 inhibited proliferation and migration of H1299 cells (all P<0.01). The Dualluciferase reporter gene assay confirmed that miR-93 could target EphA4. Overexpression of miR-93 down-regulated the mRNA and protein expression levels of EphA4(allP<0.05), and promoted proliferation and migration of H460 cells through targeted regulation of EphA4 and activation of ERK pathway (all P<0.01). Conclusion: miR-93 promotes the proliferation and migration of NSCLC cells, and its mechanism may be related to the targeted regulation of EphA4 and activation of the ERK pathway.