Hsa_circ_0049396 inhibited oral squamous cell carcinoma progression by regulating the miR-663b/ENDOU axis

Abstract

BackgroundCircular RNA (circRNAs) play an important role in oral squamous cell carcinoma (OSCC) progression and has been widely reported. In this study, we aimed to investigate the role of a novel circRNA, circ_0049396, and its underlying mechanism in OSCC. MethodsThe expression levels of circ_0049396, miR-663b, and theuridylate-specific endoribonuclease (ENDOU) were assessed by quantitative reverse transcription PCR (qRT-PCR). Cell proliferation and migration were evaluated using CCK-8 and Transwell assays, respectively. Western blotting was performed to measure the levels of the apoptosis-associated proteins (Bcl-2 and Bax). The functional role of circ _0049396 was further validated in a xenograft experiment in vivo. The interactions of miR-663b with circ_0049396/ENDOU were verified using the dual luciferase reporter, RNA pull-down, and RNA immunoprecipitation (RIP) assays. ResultsThe expression of circ_0049396 and ENDOU was downregulated in OSCC tissues and cells, whereas miR-663b was upregulated. Circ_0049396 overexpression weakened OSCC cell proliferation and migration but enhanced their apoptosis. Circ_0049396 overexpression suppresses tumorigenesis in vivo. The circ_0049396/miR-663b/ENDOU regulatory network predicted through bioinformatic analysis was validated using RNA pull-down, luciferase reporter, and RIP experiments. MiR-663b mimic enhanced the migratory and proliferative abilities of OSCC cells, but suppressed apoptosis. Furthermore, circ_0049396 or ENDOU overexpression partially reversed the malignant behavior of miR-663b-overexpressing OSCC cells. ConclusionsOur study illustrated that circ_0049396 overexpression inhibited the malignant behavior of OSCC cells by regulating the miR-663b/ENDOU axis. Based on our findings, circ_0049396 can be used as a potential therapeutic agent for OSCC.