MicroRNA-218 inhibits melanogenesis by directly suppressing microphthalmia-associated transcription factor expression.
The microphthalmia-associated transcription factor (MITF) is a pivotal regulator of melanogenic enzymes for melanogenesis, and its expression is modulated by many transcriptional factors at the transcriptional level or post-transcriptional level through microRNAs (miRNAs). Although several miRNAs modulate melanogenic activities, there is no evidence of their direct action on MITF expression. Out of eight miRNAs targeting the 3'-UTR of Mitf predicted by bioinformatic programs, our results show miR-218 to be a novel candidate for direct action on MITF expression. Ectopic miR-218 dramatically reduced MITF expression, suppressed tyrosinase activity, and induced depigmentation in murine immortalized melan-a melanocytes. MiR-218 also suppressed melanogenesis in human pigmented skin organotypic culture (OTC) through the repression of MITF. An inverse correlation between MITF and miR-218 expression was found in human primary skin melanocytes and melanoma cell lines. Taken together, our findings demonstrate a novel mechanism involving miR-218 in the regulation of the MITF pigmentary process and its potential application for skin whitening therapy.
School of Biomedical Sciences; Faculty of Medicine; The Chinese University of Hong Kong; Hong Kong, P.R. China.
Jia
J
Guo
School of Biomedical Sciences; Faculty of Medicine; The Chinese University of Hong Kong; Hong Kong, P.R. China; Shenzhen Research Institute; The Chinese University of Hong Kong; Hong Kong, P.R. China.
Jin-fang
JF
Zhang
School of Biomedical Sciences; Faculty of Medicine; The Chinese University of Hong Kong; Hong Kong, P.R. China.
Wei-mao
WM
Wang
School of Biomedical Sciences; Faculty of Medicine; The Chinese University of Hong Kong; Hong Kong, P.R. China.
Florence Wing-ki
FW
Cheung
Guangzhou Institute of Advanced Technology; Chinese Academy of Sciences; P.R. China.
Ying-fei
YF
Lu
Division of Urology; Department of Surgery; Prince of Wales Hospital; The Chinese University of Hong Kong; Hong Kong, P.R. China.
Chi-fai
CF
Ng
School of Biomedical Sciences; Faculty of Medicine; The Chinese University of Hong Kong; Hong Kong, P.R. China.
Hsiang-fu
HF
Kung
School of Biomedical Sciences; Faculty of Medicine; The Chinese University of Hong Kong; Hong Kong, P.R. China.
Wing-keung
WK
Liu
D020413:3' Untranslated Regions; D000818:Animals; D020029:Base Pairing; D001483:Base Sequence; D001665:Binding Sites; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D019295:Computational Biology; D030561:Databases, Nucleic Acid; D005786:Gene Expression Regulation; D006801:Humans; D008543:Melanins / Q000096:biosynthesis / Q000235:genetics*; D008544:Melanocytes / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics*; D051739:Microphthalmia-Associated Transcription Factor / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D046509:Tissue Culture Techniques
D020413:3' Untranslated Regions; D008543:Melanins; D035683:MicroRNAs; D051739:Microphthalmia-Associated Transcription Factor
melanogenesis; microRNA-218; microphthalmia-associated transcription factor (MITF); tyrosinase (TYR)