Silencing of circ_OSBPL10 affects the functional behaviors of oral squamous cell carcinoma cells by the miR-299-3p/CDK6 axis

Abstract

BackgroundCircular RNAs (circRNAs) are increasingly implicated in the development of oral squamous cell carcinoma (OSCC). Here, we explored the precise role of circRNA oxysterol binding protein like 10 (circ_OSBPL10, circ_0008549) in OSCC pathogenesis. MethodsRibonuclease (RNase) R assay was performed to assess the stability of circ_OSBPL10. The levels of circ_OSBPL10, microRNA (miR)-299-3p and cyclin-dependent kinase 6 (CDK6) mRNA were gauged by qRT-PCR. CDK6 protein level was measured by western blot. Cell proliferation was detected by MTT and colony formation assays. Cell cycle distribution and apoptosis were measured by flow cytometry. Cell migration and invasion were evaluated using transwell assay. Dual-luciferase reporter assay was used to identify the relationship between miR-299-3p and circ_OSBPL10 or CDK6. Animal studies were performed to evaluate the role of circ_OSBPL10 in tumor growth in vivo. ResultsCirc_OSBPL10 was up-regulated in OSCC tissues and cells. Silencing of circ_OSBPL10 hindered cell proliferation, cell cycle progression, colony formation, migration, invasion, and promoted apoptosis in vitro and diminished tumor growth in vivo. Mechanistically, circ_OSBPL10 directly targeted miR-299-3p, and circ_OSBPL10 silencing affected cell functional properties in vitro by up-regulating miR-299-3p. CDK6 was a direct and functional target of miR-299-3p. The circ_OSBPL10/miR-299-3p axis regulated cell functional properties in vitro via CDK6. Moreover, circ_OSBPL10 acted as a competing endogenous RNA (ceRNA) to regulate CDK6 expression through miR-299-3p. ConclusionOur present findings first demonstrate that circ_OSBPL10 can regulate the functional behaviors of OSCC cells at least partially by miR-299-3p/CDK6 axis, highlighting circ_OSBPL10 as a promising therapeutic target for OSCC.