MicroRNA‑199a‑5p suppresses migration and invasion in oral squamous cell carcinoma through inhibiting the EMT‑related transcription factor SOX4.

Abstract

MicroRNAs (miRs) are small, non-coding RNAs that can act as oncogenes or tumor suppressor genes in human cancer. Recent studies have revealed that miR-199a-5p is abnormally expressed in various types of human cancer; however, the potential role of miR-199a-5p in oral squamous cell carcinoma (OSCC) remains elusive. The present study investigated the role of miR-199a-5p in OSCC cells and explored the potential molecular mechanism. Reverse transcription-quantitative polymerase chain reaction was used to measure miR-199a-5p expression in OSCC tissues and adjacent normal oral epithelial tissues. Cell invasion and migration were evaluated using Transwell invasion and wound-healing assays in OSCC cells post-transfection with miR-199a-5p mimics or negative control mimics. In addition, a luciferase reporter assay was conducted to identify the target gene of miR-199a-5p in OSCC cells. The results demonstrated that miR-199a-5p expression was significantly downregulated in OSCC tissues and cell lines, and was associated with tumor progression in OSCC. Furthermore, overexpression of miR-199a-5p inhibited cell invasion and migration, and blocked the epithelial-mesenchymal transition (EMT) cascade. Notably, the results revealed that the EMT-related transcription factor SRY-box 4 (SOX4) was a direct target gene of miR-199a-5p, as determined by the direct binding of miR-199a-5p with the 3′-untranslated region of SOX4. In addition, knockdown of SOX4 by small interfering RNA-SOX4 suppressed proliferation, migration and invasion of OSCC cells. Conversely, overexpression of SOX4 rescued the suppressive effects of miR-199a-5p on cell migration and invasion. Collectively, these data indicated that miR-199a-5p may inhibit the migration and invasion of OSCC cells via targeting the EMT-related transcription factor SOX4, thus suggesting that miR-199a-5p may serve as a prognostic biomarker and therapeutic target in the treatment of OSCC.