MicroRNA-141-3p and microRNA-200a-3p regulate α-melanocyte stimulating hormone-stimulated melanogenesis by directly targeting microphthalmia-associated transcription factor

In recent years, it has been reported that non-coding RNAs, especially microRNAs (miRNAs) and long non-coding RNAs, act as melanogenesis-regulating molecules in melanocytes. We found that the expression levels of miR-141-3p and miR-200a-3p were decreased significantly by α-melanocyte stimulating hormone (α-MSH) stimulation in mouse melanocyte B16-4A5 cells, as demonstrated by a miRNA array. Overexpression of miR-141-3p and miR-200a-3p in B16-4A5 cells suppressed melanogenesis and tyrosinase activity. Moreover, both miR-141-3p and miR-200a-3p showed direct targeting of microphthalmia-associated transcription factor using a luciferase reporter assay. Furthermore, topical transfection of miR-141-3p and miR-200a-3p to three-dimensional reconstructed human skin tissue inhibited α-MSH-stimulated melanin biosynthesis. Taken together, our findings indicate that down regulation of miR-141-3p and miR-200a-3p during the α-MSH-stimulated melanogenesis process acts as an important intrinsic signal. This result is expected to lead to the development of miRNA-based whitening therapeutics.

alpha-melanocyte stimulating hormone (α-MSH), melanogenesis, MelanoDerm (MEL-300-B), EPI-100-LLMM, melanin content, microphthalmia-associated transcription factor (Mitf), tyrosinase, skin lightening, topical transfection, microRNA (miRNA), skin whitening

miR-141-3p, miR-200a-3p, microRNA