CircZNF236 facilitates malignant progression in oral squamous cell carcinoma by sequestering miR-145-5p.

BACKGROUND: A number of non-coding circular RNAs (circRNAs) have recently been implicated in the modulation of gene expression in cancer models. We therefore sought to explore if circZNF236 has a role in oral squamous cell carcinoma (OSCC). METHODS: We first examined circZNF236 expression in 32 pairs of OSCC and noncancerous tissues. We then investigated a functional role for circZNF236 using knockdown and overexpression approaches in OSCC cancer cell lines. Cell counting kit-8, wound healing, Transwell, and flow cytometry were employed to assess circZNF236 function in vitro. The association between circZNF236 and miR-145-5p, or that between miR-145-5p and malignant brain tumor domain containing 1 (MBTD1) was predicted by bioinformatics and demonstrated by dual-luciferase reporter assays, RNA pull-down assays as well as RNA immunoprecipitation (RIP) assays. A mouse OSCC xenograft model was employed to demonstrate the impacts of circZNF236 inhibition on tumor development in vivo. RESULTS: OSCC tissues and cells had higher levels of circZNF236 expression compared with normal controls. Furthermore, high circZNF236 levels in patients with OSCC correlated with a poor prognosis. CircZNF236 silencing decreased the malignant properties of OSCC cells and suppressed OSCC tumor formation in the mouse model. We then noticed that miR-145-5p can be regulated by circZNF236, and that circZNF2361 promoted OSCC development by absorbing miR-145-5p and consequently upregulating MBTD1 expression. CONCLUSION: CircZNF236 modulates OSCC via the miR-145-5p/MBTD1 axis. These results support the potential of circZNF236 as a treatment target for OSCC.