A new target for the treatment of oral squamous cell carcinoma: Circ_0046336

Background This study was designed to investigate the mechanism of Circ_0046336 in oral squamous cell carcinoma (OSCC). Methods The expression pattern of Circ_0046336 and its distribution in OSCC cell lines (SCC-9 and CAL-27) were identified. Fluorescence in situ hybridization was applied to determine the location of Circ_0046336. Circ_0046336 silencing was detected by methylthiazolyldiphenyl-tetrazolium bromide (MTT), flow cytometry and transwell assays. The binding relation between Circ_0046336 and miR-181d-3p or ADAM12 and miR-181d-3p was investigated using bioinformatics and dual luciferase reporter assay. ADAM12 and miR-181d-3p expressions in OSCC cells with Circ_0046336 knockdown were quantified. Rescue assays were carried out, and the expressions of epithelial-mesenchymal transition (EMT)-related proteins were measured via Western blot. Results Circ_0046336 was overexpressed and mainly distributed in the cytoplasm of OSCC cells. Circ_0046336 targeted miR-181d-3p and miR-181d-3p targeted ADAM12 in OSCC cells. Circ_0046336 silencing facilitated apoptosis, and suppressed viability, migration and invasion of OSCC cells, while upregulating miR-181d-3p and downregulating ADAM12. MiR-181d-3p deficiency reversed the regulatory role of Circ_0046336 in biological behaviors of OSCC cells. Circ_0046336 silencing promoted E-cadherin expression and inhibited N-cadherin and Vimentin expressions, but such effects were reversed by miR-181d-3p downregulation. Conclusion Circ_0046336 acts as a ceRNA to regulate apoptosis, migration, invasion and EMT of OSCC cells via miR-181d-3p/ADAM12 axis.