Circular RNA CircFADS2 Inhibits the Progression of Cutaneous Squamous Cell Carcinoma by Regulating MiR-766-3p/HOXA9 Axis

Background: Mounting evidence indicates that circular RNAs (circRNAs) play vital roles in human diseases, especially in cancers. However, the biological functions and underlying mechanism of circRNA fatty acid desaturase 2 (circFADS2) in cutaneous squamous cell carcinoma (CSCC) have not been reported.

Methods: The expression levels of circFADS2, microRNA-766-3p (miR-766-3p) and homeobox A9 (HOXA9) were determined by quantitative real-time PCR (qRT-PCR). Flow cytometry analysis was used to determine cell cycle distribution. Cell proliferation was evaluated by Cell Counting Kit-8 (CCK-8) and colony formation assays. Wound healing and transwell assays were used to assess cell migration and invasion abilities. Glycolysis was examined via the measurement of extracellular acidification rate (ECAR). All protein levels were detected by western blot assay. The interaction between miR-766-3p and circFADS2 or HOXA9 was predicted by bioinformatics software and confirmed by dual-luciferase reporter, RNA pull-down, and RNA Immunoprecipitation (RIP) assays. The mouse xenograft model was established to investigate the role of circFADS2 in vivo.

Results: CircFADS2 was downregulated in CSCC tissues and cells. CircFADS2 overexpression inhibited CSCC cell proliferation, metastasis and glycolysis. Moreover, miR-766-3p was able to directly bind to circFADS2, and circFADS2 played an anti-cancer role in CSCC by downregulating miR-766-3p. In addition, HOXA9 was a direct target of miR-766-3p, and miR-766-3p inhibition suppressed CSCC cell proliferation, metastasis and glycolysis by upregulating HOXA9. Furthermore, circFADS2 acted as a sponge of miR-766-3p to regulate HOXA9 expression. Besides, circFADS2 suppressed tumor growth in vivo.

Conclusion: CircFADS2 suppressed CSCC progression by regulating miR-766-3p/HOXA9 axis, which might provide a promising therapeutic target for CSCC.