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

Abstract

BackgroundMelanocytes 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.ResultsIn 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.ConclusionsThe 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.

Long non-coding RNA LRRC75A-AS1 facilitates triple negative breast cancer cell proliferation and invasion via functioning as a ceRNA to modulate BAALC

“…According to previous findings, miR-380–3p regulated by Nrf2 suppressed cell proliferation and strengthened the PQ-induced toxicity in mouse neuroblastoma cells via obstructing Sp3 mRNA translation 30 . MiR-380–3p could modulate melanogenesis via targeting SOX6 in melanocytes 31 . Herein, our research firstly revealed the anti-tumor function of miR-380–3p in TNBC.…”

Role of ATF3 as a prognostic biomarker and correlation of ATF3 expression with macrophage infiltration in hepatocellular carcinoma

“…Our study also identified several miRNAs involved in transcriptional regulation and carcinogenesis. MiR-380-3p was shown to target SOX6 to regulate bactericidal effects by affecting β-catenin MITF transcription and translation, providing insights into the mechanisms by which miR-380-3p controls melanogenesis [39]. To further clarify genetic alterations, functions, and carcinogenic mechanisms of ATF3, we evaluated the frequency of ATF3 mutations in HCC and obtained an estimate of 10% based on publicly available data.…”

Role of ATF3 as a prognostic biomarker and correlation of ATF3 expression with macrophage infiltration in hepatocellular carcinoma

“…Our study also identi ed several miRNAs involved in transcriptional regulation and carcinogenesis. MiR-380-3p was shown to target SOX6 to regulate bactericidal effects by affecting βcatenin MITF transcription and translation, providing insights into the mechanisms by which miR-380-3p controls melanogenesis [30]. To further clarify genetic alterations, functions, and carcinogenic mechanisms of ATF3, we evaluated the frequency of ATF3 mutations in HCC and obtained an estimate of 10% based on publicly available data.…”