Circ_0017956 promotes the proliferation and metastasis of non-small cell lung cancer through regulating miR-515-5p/ITGB8 axis. 2021

Na Li, and Dan Zhu
Department of Respiratory, The Second Affiliated Hospital of Dalian Medical University, Dalian, China.

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.

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