Downregulated microRNA-149-3p triggers malignant development and predicts worse prognosis in oral squamous cell carcinoma

Abstract

Objective: Accumulating evidence reveals that aberrant expression of microRNAs contributes to the tumorigenesis and development of diverse human cancers. In the current study, we aimed to evaluate the functional role and prognostic value of miR-149-3p in oral squamous cell carcinoma (OSCC).

Methods: Real-time polymerase chain reaction (PCR) analysis was performed to detect the expression of miR-149-3p in 70 OSCC patients (64.10 ± 11.97 years; 31 males and 39 females). The prognostic ability of miR-149-3p in OSCC patients was assessed by Kaplan-Meier survival analysis. Transwell assays and cell adhesion assays were used to investigate the impact of miR-149-3p on cell migration and invasion. The regulation of MMP2 expression by miR-149-3p was determined by real-time PCR, western blotting and dual luciferase reporter assay.

Results: Our results revealed a lower level of miR-149-3p in OSCC tissues than in adjacent normal tissues. Downregulation of miR-149-3p was correlated with malignant development and poor outcomes in patients with OSCC. MiR-149-3p repressed the migratory and invasive abilities of OSCC cells. We confirmed that miR-149-3p targeted the 3'-untranslated region of MMP2 mRNA to suppress MMP2 expression. Moreover, the miR-149-3p-mediated decrease in metastasis was reversed by overexpression of MMP2 in OSCC cells.

Conclusion: Our findings provide an important molecular mechanism by which miR-149-3p inhibits OSCC cell migration and invasion via negative regulation of MMP2 and implicate miR-149-3p as a prospective biomarker and therapeutic target for OSCC.

Keywords: MMP2; MicroRNA-149-3p; Oral squamous cell carcinoma; Prognosis; Progression.