ABCB6 knockdown suppresses melanogenesis through the GSK3-β/β-catenin signaling axis in human melanoma and melanocyte cell lines

Background: Melanogenesis is a multistep process in which melanocytes produce melanin pigments within melanosomes. However, the roles played by the biological factors and pathways in this process are not yet fully understood. Objective: To investigate the role of ATP-binding cassette subfamily B member 6 (ABCB6) in the regulation of melanogenesis in vitro. Methods: Real-time PCR and western blotting were used to assess the knockdown efficiency of ABCB6 in MNT-1 and PIG1 stable cell lines. Cleavage by NaOH was used to determine melanin content, while the number of melanosomes was examined for each stage by transmission electron microscopy. Immunofluorescence microscopy was used to evaluate endogenous protein location. Differentially expressed genes were detected using RNA sequencing, and gene expression was assessed by quantitative real-time PCR. KEGG mapping was used for pathway enrichment analysis. Co-immunoprecipitation was used for protein-protein interactions analysis. Results: We found that ABCB6 inhibition could impair melanocyte maturation and melanin production in human melanoma (MNT-1) and immortalized human melanocyte (PIG1) cell lines. Moreover, ABCB6 knockdown inhibited the protein expression of melanocyte inducing microphthalmia-associated transcription factor (MITF) and its three downstream melanogenic enzymes (TYR, TYRP1 and TYRP2). Mechanistically, we revealed that ABCB6 could interact with and modulate glycogen synthase kinase 3 beta (GSK3-beta) to exert its biological effect on melanogenesis. Conclusion: Our findings suggest that ABCB6 is a key regulator of melanogenesis via the GSK3-pip-catenin signaling pathway. However, further in-depth studies are essential to uncover the relationship between ABCB6 and pigmentation disorders. (C) 2022 The Author(s). Published by Elsevier B.V. on behalf of Japanese Society for Investigative Dermatology.

Automated summary

This study investigates the role of ATP-binding cassette subfamily B member 6 (ABCB6) in melanogenesis. The findings suggest that ABCB6 inhibition impairs melanocyte maturation and melanin production in human melanoma and immortalized human melanocyte cell lines. Mechanistically, ABCB6 interacts with and modulates glycogen synthase kinase 3 beta (GSK3-beta) to exert its biological effect on melanogenesis. Further studies are necessary to uncover the relationship between ABCB6 and pigmentation disorders.