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.
Highlights
Human skin comprises approximately 15% of the total body weight and performs many important functions for maintaining body homeostasis
MiR-31 is highly expressed in psoriatic skin keratinocytes and modulates cytokine/chemokine expression such as interleukin (IL)-1β, C-X-C motif chemokine ligand (CXCL) 1, CXCL5, and CXCL8/IL-8 via the direct targeting of serine/threonine kinase 40, which is a negative regulator of nuclear factor-kappa B20
To confirm the results from the miRNA array analysis, we examined the expression levels of miR-141-3p and miR-200a-3p in α-melanocytestimulating hormone (α-MSH)-stimulated and non-treated B16-4A5 cells by the quantitative real-time polymerase chain reaction
Summary
Human skin comprises approximately 15% of the total body weight and performs many important functions for maintaining body homeostasis. MicroRNAs (miRNAs) are a class of small non-coding RNAs that are 18 to 25 base-pair single-strand RNA molecules They play pivotal roles in regulating gene expression, mainly at the post-transcriptional level. With respect to pigmentation of the skin, numerous miRNAs regulate enzymes for melanin synthesis and melanogenesis signalling molecules[24,25,26,27,28]. Many of these target MITF and regulate the mRNA levels of enzymes for melanin synthesis. The findings establish that modulating both miR141-3p and miR-200a-3p may be a potential strategy for treating skin pigmentation disorders or whitening
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