Background The regulation of melanogenesis has been investigated as a long-held aim for pharmaceutical manipulations with denotations for malignancy of melanoma. Mucins have a protective function in epithelial organs; however, in the most outer organ, the skin, the role of mucins has not been studied enough. Objectives Our initial hypothesis developed from the identification of correlations between pigmentation and expressions of skin mucins, particularly those existing in skin tissue. We aimed to investigate the action of mucins in human melanocytic cells.
Materials and methodsThe expression of mucin proteins in human skin was investigated using microarray data from the Human Protein Atlas consortium (HPA) and the Genotype-Tissue Expression consortium (GTEx) database. Mucin expression was measured at RNA and protein levels in melanoma cells. The findings were further validated and confirmed by analysis of independent experiments. Results We found that the several mucin proteins showed expression in human skin cells and among these, mucin-like protein 1 (MUCL1) showed the highest expression and also clear negative correlation with melanogenesis in epidermal melanocytes. We confirmed the correlations between melanogenesis and MUCL1 by revealing negative correlations in melanocytes with different melanin production, resulting from increased composition of threonine, mucin-conforming amino acid, and increased autophagy-related forkhead-box O signalling. Furthermore, threonine itself affects melanogenesis and metastatic activity in melanoma cells. Conclusions We identified a significant association between MUCL1 and threonine with melanogenesis and metastasis-related genes in melanoma cells. Our results define a novel mechanism of mucin regulation, suggesting diagnostic and preventive roles of MUCL1 in cutaneous melanoma.What is already known about this topic?• Despite considerable advances in radioactive therapeutics or chemotherapeutic approaches for the treatment of abnormal melanogenesis, there are still many caveats to delivery, effectiveness and safety, thus leaving a necessity for more immediate pharmaceutical targets.• Mucins have protective and chemical barrier functions in epithelial organs; however, in the skin, mucin has scarce expression and is known only as a diagnostic aid in skin disorders such as mucinosis.What does this study add?• We provide detailed analysis demonstrating the potential of mucin-like protein 1 (MUCL1), which showed negative correlations in melanocytes with different