Circular RNA ITCH Suppresses Cell Proliferation but Induces Apoptosis in Oral Squamous Cell Carcinoma by Regulating miR-421/PDCD4 Axis

BACKGROUND: Circular RNAs (circRNAs), a group of covalently closed non-coding RNAs, serve critical regulatory roles in many human cancers, including oral squamous cell carcinoma (OSCC). The purpose of this study was to investigate the functional role of circular RNA ITCH (circ-ITCH) in OSCC and the underlying mechanisms. METHODS: RT-qPCR analysis was applied to detect the expression levels of circ-ITCH in OSCC tissues and cell lines. MTT assay and flow cytometer analysis were used to evaluate the effects of circ-ITCH overexpression on the proliferation and apoptosis of OSCC cells. Bioinformatics analysis and dual-luciferase reporter assay were applied to determine the binding relation between circ-ITCH and miR-421 as well as PDCD4 mRNA and miR-421. RESULTS: Our results showed that circ-ITCH expression was remarkably decreased in OSCC tissues and cell lines. Low circ-ITCH expression was strongly associated with adverse clinicopathological characteristics of OSCC patients. Moreover, functional assays demonstrated that circ-ITCH overexpression significantly inhibited OSCC cell proliferation and induced cell apoptosis. Our data further uncovered that circ-ITCH could bind directly to miR-421 and block its repression on PDCD4 in OSCC. MiR-421 expression was significantly increased in OSCC tissues and was inversely correlated with circ-ITCH expression. Notably, miR-421 restoration blocked the tumor-suppressive role of circ-ITCH in OSCC cells. CONCLUSION: In conclusion, our study reveals that circ-ITCH serves as a tumor suppressor in OSCC partly by regulating miR-421/PDCD4 axis.