Decreased miR-146a is associated with aggressive human oral squamous cell carcinoma.

With the aim to identify microRNAs that may contribute to oral squamous cell carcinoma (OSCC) progression,we compared the microRNA expression profiles of two related cell lines that form tumors with differential aggressiveness. A panel of 28 microRNAs was found to be more than 1.5-fold altered,among which miR-146a was the most significantly changed (-4.6-fold). Loss of miR-146a expression was validated in human high-grade tumors,while normal oral mucosa retained expression,using fluorescence in situ hybridization on a tissue microarray. Restoration of miR-146a in SCC25 and UMSCC1 cells decreased in vitro invasive activity,suppressed tumor growth in vivo,and decreased the incidence of UMSCC1 lung metastasis. The transcription factor Sox2 was found to be a putative target of miR-146a. In conclusion,the loss or decrease of miR-146a is a new feature that is associated with more aggressive behaviour in oral squamous carcinoma.