MicroRNA-149-3p inhibits cell proliferation by targeting AKT2 in oral squamous cell carcinoma

MicroRNAs (miRs) exhibit oncogenic or tumor suppressive functions that contribute to the initiation and development of various types of human cancer. miR-149-3p has been reported to serve multiple roles in the regulation of proliferation, apoptosis and metastasis. However, the effects and detailed mechanism of miR-149-3p in oral squamous cell carcinoma (OSCC) remain unclear. In the present study, miR-149-3p mimic, mimic control, miR-149-3p inhibitor and inhibitor control were transiently transfected into Cal27 and SCC-9 cells. The viability, proliferation and apoptosis of OSCC cells were determined using Cell Counting Kit-8, colony formation and Annexin V assays, respectively. The mRNA expression levels of miR-149-3p and AKT2 were determined by reverse transcription-quantitative PCR. The protein expression levels of AKT2, cleaved caspase-3 and cleaved PARP were examined by western blot analysis. The binding of miR-149-3p to the AKT2 3 '-untranslated region was evaluated by a dual luciferase reporter assay. In the present study, overexpression of miR-149-3p reduced the viability and proliferation of OSCC cells. By contrast, increased cell viability and proliferation was observed in miR-149-3p-deficient OSCC cells. Dual luciferase reporter assay indicated that miR-149-3p significantly decreased the luciferase activity of the wild-type AKT2 3 '-untranslated region. Moreover, overexpression of miR-149-3p downregulated the mRNA and protein expression levels of AKT2, suggesting that miR-149-3p was a negative modulator of AKT2. Restoration of AKT2 efficiently reversed the miR-149-3p-mediated reduction in the proliferative capacity of OSCC cells. In addition, miR-149-3p enhanced the sensitivity of OSCC cells to the chemotherapeutic drug 5-fluorouracil. Taken together, the current findings revealed an inhibitory effect of miR-149-3p on the proliferation of OSCC cells through the post-transcriptional suppression of AKT2, and indicated a potential chemosensitizing function of miR-149-3p for the treatment of patients with OSCC.

Automated summary

This study revealed the negative regulatory role of miR-149-3p on AKT2 in oral squamous cell carcinoma cells, and demonstrated that miR-149-3p increased the sensitivity of cancer cells to 5-fluorouracil.