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MicroRNA-218 inhibits melanogenesis by directly suppressing microphthalmia-associated transcription factor expression
Jia Guo1, Jin-fang Zhang2, Wei-mao Wang1
1School of Biomedical Sciences; Faculty of Medicine; The Chinese University of Hong Kong; Hong Kong, P.R. China.
Abstract:
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.
Insights
MicroRNA-218 directly targets and reduces microphthalmia-associated transcription factor (MITF) expression, suppressing melanogenesis. This finding reveals a novel mechanism for controlling pigmentation and offers potential for skin whitening therapies.
Area of Science:
- Molecular Biology
- Dermatology
- Genetics
Background:
- Microphthalmia-associated transcription factor (MITF) regulates melanogenesis.
- MicroRNAs (miRNAs) can modulate gene expression, including MITF, but direct regulation of MITF by miRNAs is not well-established.
Purpose of the Study:
- To investigate the direct role of specific miRNAs in regulating MITF expression.
- To identify novel miRNAs involved in the control of melanogenesis.
Main Methods:
- Bioinformatic prediction of miRNAs targeting MITF 3'-UTR.
- Ectopic expression of miR-218 in melanocytes and skin organotypic cultures.
- Measurement of MITF expression, tyrosinase activity, and pigmentation.
- Correlation analysis of MITF and miR-218 expression in human cells.
Main Results:
- miR-218 was identified as a direct regulator of MITF.
- Ectopic miR-218 suppressed MITF expression, tyrosinase activity, and induced depigmentation in murine melanocytes.
- miR-218 repressed melanogenesis in human skin organotypic cultures by downregulating MITF.
- An inverse correlation between MITF and miR-218 expression was observed in human skin cells.
Conclusions:
- miR-218 directly regulates MITF expression, impacting melanogenesis.
- This novel miR-218/MITF pathway offers a potential therapeutic target for skin whitening treatments.
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