MicroRNA-488-3p sensitizes malignant melanoma cells to cisplatin by targeting PRKDC.

Abstract

Deregulation of microRNAs (miRNAs) has been implicated in drug resistance in various types of cancers, including malignant melanoma (MM). MiR-488-3p has been reported as a tumor suppressor in several cancers. However, the exact expression patterns of miR-488-3p and the precise molecular mechanisms underlying its role in MM remain largely unknown and require further investigation. In this study, we demonstrated that miR-488-3p is significantly downregulated in MM clinical specimens and cell lines. Ectopic expression of miR-488-3p resulted in markedly increased drug sensitivity of MM cells in vitro and in vivo. The DNA-activated, catalytic polypeptide (PRKDC), which encodes DNA-dependent protein kinase catalytic subunit (DNA-PKcs), was identified as a direct target of miR-488-3p using luciferase reporter assays, qRT-PCR, and western blotting analyses. PRKDC knockdown by small interfering RNA (siRNA) alone promoted sensitivity of MM cells to cisplatin (DDP) while overexpression of PRKDC partially rescued the miR-488-3p-mediated acceleration of sensitivity to DDP in MM cells. Taken together, our results indicate that miR-488-3p serves as a drug resistance sensitizer in MM, supporting its potential as a promising therapeutic candidate.