Functional elucidation of the EIF4A3–circR-4225–miR-507–TNFSF11 regulatory axis in LUAD and its role in tumor progression

Abstract

Lung adenocarcinoma (LUAD) is the most common subtypes of NSCLC. However, the therapeutic effects for LUAD are unsatisfactory at current stage, so it is important to find new molecular targets and therapeutic strategies. circRNAs can regulate the expression of target genes by binding to microRNAs (miRNAs) to form competitive endogenous RNAs (ceRNAs). Therefore, we investigated the functions of circR-4225 in the tumor progression of LUAD and its molecular mechanism in this paper. circR-4225 is up-regulated in LUAD tissues. EIF4A3, a member of the eukaryotic translation initiation factor 4A (EIF4A) family, promotes the expression of circR-4225. circR-4225 acts as a molecular sponge to down-regulate miR-507, which promotes the up-regulation of the expression of its target gene–tumor necrosis factor superfamily member 11 (TNFSF11). Knockdown of circR-4225 in the LUAD cell lines can inhibit cell proliferation and viability, and promote apoptosis of the LUAD cell lines, which can be reverted by inhibiting miR-507 or overexpressing TNFSF11. To sum it up, this study demonstrated that circR-4225 was significantly up-regulated in LUAD tissues, and circR-4225 promoted LUAD progression by sponging miR-507 and up-regulating TNFSF11. This study can provide new molecular targets for early diagnosis and treatment of LUAD.