Investigating the role and mechanism of microRNA-196a in oral squamous cell carcinoma by targeting FOXO1

Oral squamous cell carcinoma (OSCC) is one of the most prevalent malignancies worldwide. MicroRNAs (miRNAs or miRs) serve crucial roles in the development of OSCC. miR-196a is upregulated in various tumors; however, the role of miR-196a in OSCC remains unclear. This present study aimed to determine the role and underlying mechanism of miR-196a in OSCC cells. Reverse transcription-quantitative PCR (RT-qPCR) was used to measure miR-196a levels in OSCC cells. MTT assays were also performed to determine cell proliferation. Cell migration was detected using wound healing assays and transwell assays, and cell apoptosis was analyzed via flow cytometry. The results indicated that the expression of miR-196a was increased in OSCC cells compared with normal oral squamous cells. TargetScan and luciferase reporter assays also confirmed that forkhead box O1 (FOXO1) was a target gene of miR-196a. It was demonstrated that FOXO1 small interfering RNA significantly promoted SCC9 cell proliferation and migration, and inhibited cell apoptosis. Furthermore, inhibition of miR-196a suppressed SCC9 cell proliferation and migration, and induced cell apoptosis. However, all effects of the miR-196a inhibitor were reversed following FOXO1 inhibition. Western blotting and RT-qPCR were subsequently performed to determine the effect of miR-196a on the PI3K/Akt signaling pathway. In the present study, transfection of miR-196a inhibitor suppressed the expression of phosphorylated (p)-PI3K and p-Akt, and enhanced the levels of FOXO1, while inhibition of FOXO1 exerted the opposite effects. Furthermore, it was demonstrated that miR-196a mimic significantly enhanced SCC9 cell proliferation and migration, and inhibited cell apoptosis. In conclusion, the results indicated that miR-196a serve as an oncogene in OSCCs. Downregulation of miR-196a inhibited the malignant biological processes of OSCC cells by targeting FOXO1. The current results may provide a novel therapeutic strategy for the treatment of patients with OSCC.