MicroRNAs are major post-transcriptional regulators responsible for the development of human
cancers, including OSCC. The specific role of
miR-619-5p in OSCC, however, is rarely reported.
Cisplatin is one of the mostly applied
chemotherapy drugs of OSCC. Nevertheless, drug resistance of
cisplatin following the initial
chemotherapy largely restricts its clinical benefits, and the mechanism of
cisplatin resistance is unclear. This study intends to explore the biological function of
miR-619-5p in the development of
cisplatin resistance in OSCC cell lines and a xenograft model, as well as the potential molecular mechanism. Our results showed that
miR-619-5p was down-regulated in OSCC samples and
cisplatin-resistant OSCC cells. Ectopically expressed
miR-619-5p inhibited proliferative, migratory and invasive abilities of OSCC
cisplatin-resistant cells. The putative target gene ATXN3 was predicted by bioinformatic analysis and confirmed by dual-
luciferase reporter assay. Importantly, ATXN3 was responsible for the regulatory effects of
miR-619-5p on biological behaviors of
cisplatin-resistant OSCC cells. Moreover,
miR-619-5p mimics and ATXN3-siRNA significantly enhanced ATXN3 knockdown in both HN6/CDDPR and CAL27/CDDPR cells and inhibited expression of PI3K and AKT. In vivo evidences demonstrated that intratumoral injection of
miR-619-5p agomir remarkably slowed down the growth of OSCC in xenograft mice. Collectively, microRNA-619-5p was the vital regulator for regulating
cisplatin resistance of OSCC, which may be served as a potential therapeutic target.