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

microRNA-141-3p 和 microRNA-200a-3p 通过直接靶向小眼畸形相关转录因子来调节 α-黑素细胞刺激激素刺激的黑素生成

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作者:Tomohiro Itoh, Kanako Fukatani, Ayaka Nakashima, Kengo Suzuki

Abstract

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 downregulation 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.

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