Quercetin suppresses the tumorigenesis of oral squamous cell carcinoma by regulating microRNA-22/WNT1/β-catenin axis.

Quercetin has potential pharmacological values in various carcinomas including oral squamous cell carcinoma (OSCC). Moreover, the anti-tumor effect of quercetin is correlated with WNT/β-catenin pathway and miRNA dysregulation. In the present study, we aimed to further investigate whether quercetin can exert its anti-tumor function by regulating miR-22 together with miR-22 downstream pathway WNT1/β-catenin in OSCC. The results of Cell Counting Kit-8 (CCK-8) and flow cytometry analyses showed that quercetin treatment and miR-22 overexpression resulted in the reduction of cell viability and the increase of cell apoptotic rate in OSCC. WNT1 was a target of miR-22, which was confirmed by bioinformatics, luciferase reporter and RNA immunoprecipitation (RIP) assays. RT-qPCR assay showed that quercetin promoted miR-22 expression and suppressed WNT1 and β-catenin expression in OSCC cells, whereas this effect was abrogated by miR-22 inhibitor. Moreover, miR-22 depletion weakened quercetin-mediated viability inhibition and apoptosis increase in OSCC cells. Quercetin inhibited the growth of OSCC xenograft tumors by inducing miR-22 expression and repressing WNT1/β-catenin pathway in vivo. Taken together, quercetin hampered OSCC tumorigenesis by regulating miR-22/WNT1/β-catenin pathway in OSCC, providing a deep insight into the molecular targets of quercetin in the treatment of OSCC.