MicroRNA-199a-5p functions as a tumor suppressor in oral squamous cell carcinoma via targeting the IKKβ/NF-κB signaling pathway

摘要

MicroRNAs (miRNAs) have been shown to have a significant role in the progression of several types of cancer, including oral squamous cell carcinoma (OSCC). However, the biological function and regulatory mechanisms of miRNAs in OSCC remain to be fully elucidated. The aim of the present study was to investigate the role of miRNAs in OSCC and the relevant mechanism. Using a microarray, it was found that miRNA (miR)-199a-5p was one of the most downregulated miRNAs in OSCC tissues. A low expression of miR-199a-5p was closely associated with tumor differentiation, lymph node metastasis, tumor-node-metastasis stage, and overall survival rate. Functionally, the overexpression of miR-199a-5p suppressed cell proliferation, induced G0/G1 cell cycle arrest, and promoted the apoptosis of Tca8113 and SCC-4 cells. Subsequently, inhibitor of nuclear factor-κB (NF-κB) kinase β (IKKβ), an important regulator of NF-κB activation, was identified as a direct target of miR-199-5p. An inverse correlation was found between miR-199a-5p and IKKβ in tumor tissues. Further investigations revealed that the overexpression of IKKβ efficiently abrogated the influences caused by the overexpression of miR-199a-5p. It was also found that the miR-199a-5p-mediated anticancer effects were dependent on the inhibition of NF-κB activation. These findings indicate that miR-199a-5p functions as a tumor suppressor through regulation of the NF-κB pathway by targeting IKKβ in OSCC.