Vitiligo is a common localized or generalized skin pigmentation disorder. Endoplasmic reticulum (ER) stress may be implicated in the development of vitiligo. microRNA‑421 (miR‑421) has been reported to be dysregulated in various human tumors. However, there is no report to date on the role of miR‑421 in vitiligo development. The present study demonstrated that 3 µM tunicamycin (TM) increased the expression of the ER stress‑related proteins protein kinase RNA‑like endoplasmic reticulum kinase (PERK), α subunit of eukaryotic translation initiation factor 2 (eIF2α) and C/EBP homologous protein (CHOP) in human primary epidermal melanocytes. Moreover, TM suppressed melanocyte viability and induced apoptosis. Reverse transcription‑quantitative PCR analysis demonstrated that TM promoted miR‑421 expression in human melanocytes. Next, TargetScan and dual luciferase reporter gene assay indicated that receptor‑interacting serine/threonine kinase 1 (RIPK1) was a direct target of miR‑421. RIPK1 expression was significantly downregulated in TM‑induced human melanocytes. Subsequently, the effect of miR‑421 downregulation on the damage of human melanocytes induced by ER stress was investigated. Human melanocytes were transfected with inhibitor control, miR‑421 inhibitor, miR‑421 inhibitor + control‑short hairpin (sh)RNA, or miR‑421 inhibitor + RIPK1‑shRNA for 24 h and then treated with TM (3 µM) for 48 h. TM was found to upregulate PERK, eIF2α and CHOP protein expression in human melanocytes, which was reduced by an miR‑421 inhibitor. In addition, the miR‑421 inhibitor increased viability and reduced apoptosis in TM‑treated melanocytes. Furthermore, all these effects of the miR‑421 inhibitor on TM‑induced human melanocytes were reversed by RIPK1‑shRNA. Further analyses revealed that the miR‑421 inhibitor activated the phosphoinositide 3 kinase/protein kinase B/mammalian target of rapamycin signaling pathway in TM‑induced human melanocytes. These data collectively suggest that miR‑421 may serve as a new treatment target in vitiligo development.
Keywords: microrna-421; vitiligo; receptor-interacting serine/ threonine kinase 1; human melanocytes; endoplasmic reticulum stress.