MicroRNA-488-3p sensitizes malignant melanoma cells to cisplatin by targeting PRKDC.
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.
Department of Plastic Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, China.
Ning
N
Li
Harbin Center for Disease Control and Prevention, Harbin, 150020, China.
Yue
Y
Ma
Computer Center, Fifth Hospital of Harbin, Harbin, 150030, China.
Li
L
Ma
Animal and Plant Laboratory, Inspection and Quarantine Bureau of Heihe, Heihe, 164300, China.
Yu
Y
Guan
Computer Center, Fifth Hospital of Harbin, Harbin, 150030, China.
Liang
L
Ma
Department of Plastic Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, China.
Daping
D
Yang
D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D002945:Cisplatin / Q000494:pharmacology; D051747:DNA-Activated Protein Kinase / Q000187:drug effects*; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D055785:Gene Knockdown Techniques / Q000379:methods; D006801:Humans; D008545:Melanoma / Q000188:drug therapy / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism / Q000502:physiology* / Q000627:therapeutic use*; D009687:Nuclear Proteins / Q000187:drug effects*; D034741:RNA, Small Interfering
C561403:MIRN488 microRNA, human; D035683:MicroRNAs; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D051747:DNA-Activated Protein Kinase; C497263:PRKDC protein, human; D002945:Cisplatin
PRKDC; drug resistance; malignant melanoma; miR-488-3p