ΜicroRNA­421 participates in vitiligo development through regulating human melanocyte survival by targeting receptor­interacting serine/threonine kinase 1.

Vitiligo is a common localized or generalized skin pigmentation disorder. Endoplasmic reticulum (ER) stress may be implicated in the development of vitiligo. microRNA­421 (miR­421) has been reported to be dysregulated in various human tumors. However, there is no report to date on the role of miR­421 in vitiligo development. The present study demonstrated that 3 µM tunicamycin (TM) increased the expression of the ER stress­related proteins protein kinase RNA­like 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 transcription­quantitative PCR analysis demonstrated that TM promoted miR­421 expression in human melanocytes. Next, TargetScan and dual luciferase reporter gene assay indicated that receptor­interacting serine/threonine kinase 1 (RIPK1) was a direct target of miR­421. RIPK1 expression was significantly downregulated in TM­induced human melanocytes. Subsequently, the effect of miR­421 downregulation on the damage of human melanocytes induced by ER stress was investigated. Human melanocytes were transfected with inhibitor control, miR­421 inhibitor, miR­421 inhibitor + control­short hairpin (sh)RNA, or miR­421 inhibitor + RIPK1­shRNA 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 miR­421 inhibitor. In addition, the miR­421 inhibitor increased viability and reduced apoptosis in TM­treated melanocytes. Furthermore, all these effects of the miR­421 inhibitor on TM­induced human melanocytes were reversed by RIPK1­shRNA. Further analyses revealed that the miR­421 inhibitor activated the phosphoinositide 3 kinase/protein kinase B/mammalian target of rapamycin signaling pathway in TM­induced human melanocytes. These data collectively suggest that miR­421 may serve as a new treatment target in vitiligo development.