MiR-495/IGF-1/AKT Signaling as a Novel Axis Is Involved in the Epithelial-to-Mesenchymal Transition of Oral Squamous Cell Carcinoma.

PURPOSE

Increasing evidence suggests that aberrant expression of miR-495 is associated with the progression of various cancers. The aim of this study was to investigate the function and underlying mechanism of miR-495 in oral squamous cell carcinoma (OSCC).

MATERIALS AND METHODS

OSCC specimens and oral cancer cell lines, as well as the OSCC microRNA expression profile from the Gene Expression Omnibus database, were used to detect the expression of miR-495 in OSCC. Cell proliferation, migration, and invasion assays were performed to analyze the function of miR-495. Bioinformatics and luciferase reporter assays were used to identify the target gene of miR-495. Pearson analysis was carried out to investigate the correlation between miR-495 and insulin-like growth factor 1 (IGF1) or AKT levels. Transfection of pcDNA3.1 vector and small interfering RNA was performed to overexpress or downregulate the expression of IGF1. OSCC xenografts in mice were constructed to validate the function and mechanism of miR-495 in vivo.

RESULTS

MiR-495 was downregulated in OSCC tissues and cell lines, and it markedly inhibited cell proliferation, migration, and invasion, as well as epithelial-to-mesenchymal transition (EMT)-related proteins of OSCC cells. IGF1 was identified as a direct target gene of miR-495. Besides, AKT was confirmed to be regulated by miR-495/IGF-1 signaling, and miR-495 was negatively correlated with IGF1 and AKT in OSCC. In vivo, miR-495 inhibited the growth and EMT-related proteins of OSCC xenografts in mice.

CONCLUSIONS

The miR-495/IGF-1/AKT signaling axis played a tumor-suppressive role in OSCC by regulating cell proliferation, invasion, and migration, as well as EMT.