Circ_0017956 promotes the proliferation and metastasis of non-small cell lung cancer through regulating miR-515-5p/ITGB8 axis

Abstract

ABSTRACT Circular RNAs (circRNAs) have been reported to exert vital roles in the tumorigenesis of non-small cell lung cancer (NSCLC). The study aimed to probe the function of circ_0017956 in NSCLC development. The expression of circ_0017956, microRNA (miR)-515-5p and integrin subunit beta 8 (ITGB8) was gauged by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot. The proliferation detection was conducted employing Cell Counting Kit-8 (CCK-8) and colony formation assays. Transwell assay was performed to determine cell migratory and invasive abilities. Western blot was implemented for the measurement of related proteins. The targeted interactions among circ_0017956, miR-515-5p and ITGB8 were affirmed by dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay and RNA pull-down assay. The role of circ_0017956 in NSCLC tumor growth in vivo was studied by xenograft mice model. Circ_0017956 and ITGB8 abundances were overtly raised whereas miR-515-5p was low expressed in NSCLC tissues and cells. Circ_0017956 knockdown caused inhibitory effects on the proliferative and metastasizing capacities of NSCLC cells. Mechanistically, circ_0017956 could sponge miR-515-5p, and circ_0017956 depletion blocked NSCLC cell malignant behaviors by increasing miR-515-5p expression. Furthermore, miR-515-5p targeted ITGB8 and ITGB8 overexpression also neutralized the miR-515-5p-triggered inhibition effects on NSCLC cell progression. Moreover, circ_0017956 could regulate ITGB8 expression through sponging miR-515-5p. In addition, circ_0017956 knockdown repressed NSCLC tumorigenesis by targeting miR-515-5p/ITGB8 axis in vivo. Circ_0017956 could promote NSCLC carcinogenesis at least partly through sponging miR-515-5p and upregulating ITGB8 level, providing a novel theoretical basis for NSCLC treatment.