miR-380-3p regulates melanogenesis by targeting SOX6 in melanocytes from alpacas (Vicugna pacos)

• Published in: BMC genomics Vol. 20; no. 1; p. 962
• Main Authors: Liu, Xuexian, Du, Bin, Zhang, Pengqian, Zhang, Junzhen, Zhu, Zhiwei, Liu, Bo, Fan, Ruiwen
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 10.12.2019; BioMed Central; BMC
• Subjects: 3' Untranslated Regions; Alpaca; Animals; Antisense RNA; beta Catenin - genetics; beta Catenin - metabolism; Binding sites; Biochemistry; Biosynthesis; Camelids, New World; Cells, Cultured; Chemical reactions; Cyclin-dependent kinases; Cytoplasm; Dopachrome isomerase; Embryo cells; Enzymes; Free radicals; Gene Expression; Gene Expression Regulation; Gene Knockdown Techniques; Genes; Genomics; Hybridization; Intramolecular Oxidoreductases - genetics; Kinases; Luciferase; Male; Mammals; Melanin; Melanins - metabolism; Melanocytes; Melanocytes - metabolism; Melanogenesis; Messenger RNA; Microphthalmia-associated transcription factor; Microphthalmia-Associated Transcription Factor - genetics; Microphthalmia-Associated Transcription Factor - metabolism; MicroRNA; microRNA-380-3p; MicroRNAs - genetics; MicroRNAs - metabolism; miRNA; Monophenol Monooxygenase - genetics; Neural crest; Oxidoreductases - genetics; Phenols (Class of compounds); Plasmids; Protein expression; Proteins; Quantitative analysis; Ribonucleic acid; RNA; Sex-determining region Y-box 6; Skin; Skin - cytology; Skin - metabolism; Skin - pathology; SOXD Transcription Factors - genetics; SOXD Transcription Factors - metabolism; Stem cell transplantation; Stem cells; Transcription (Genetics); Transcription factors; Translation; Translation (Genetics); Tyrosinase; Tyrosine; Tyrosine-related protein-1; β-Catenin; China; Microphthalmia-associated transcription factor; Sex-determining region Y-box 6; microRNA-380-3p; Dopachrome tautomerase; Melanogenesis; Tyrosine-related protein-1; Tyrosinase
• ISSN: 1471-2164; 1471-2164
• DOI: 10.1186/s12864-019-6343-4

Melanocytes are derived from neural crest stem cells in the embryonic stage. In mature melanocytes, a series of complex enzyme-catalyzed reactions leads to the production of melanins, which determine the hair and skin colors of animals. The process of melanogenesis is complex and can be regulated by mRNA, microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) genes. MiRNAs are a type of endogenous noncoding RNA approximately 22 nt in size that predominantly regulate gene expression by inhibiting translation. miR-380-3p is a candidate miRNA potentially related to melanogenesis. To better understand the mechanism of miR-380-3p melanogenesis regulation, plasmids to overexpress or knockdown miR-380-3p were transfected into alpaca melanocytes, and their effects on melanogenesis were evaluated. In situ hybridization identified a positive miR-380-3p signal in alpaca melanocyte cytoplasm. Luciferase activity assays confirmed that SOX6 is targeted by miR-380-3p. miR-380-3p overexpression and knockdown in alpaca melanocytes respectively downregulated and upregulated SOX6 expression at the mRNA and protein levels. Additionally, miR-380-3p overexpression and knockdown, respectively, in alpaca melanocytes decreased and increased the mRNA levels of melanin transfer-related genes, including microphthalmia-associated transcription factor (MITF), tyrosinase (TYR), tyrosine-related protein-1 (TYRP1), and dopachrome tautomerase (DCT). In contrast, miR-380-3p overexpression and knockdown respectively increased and decreased the mRNA levels of β-catenin. Additionally, the effect of miR-380-3p on melanogenesis was assessed by Masson-Fontana melanin staining. The results demonstrated that miR-380-3p targeted SOX6 to regulate melanogenesis by influencing β-catenin and MITF transcription and translation, which reduced the expression of downstream genes, including TYR, TYRP1, and DCT. These results provide insights into the mechanisms through which miR-380-3p controls melanogenesis.