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ΜicroRNA‑421 participates in vitiligo development through regulating human melanocyte survival by targeting receptor‑interacting serine/threonine kinase 1

  • Authors:
    • Xuecheng Sun
    • Tao Wang
    • Bo Huang
    • Gaobo Ruan
    • Aie Xu
  • View Affiliations / Copyright

    Affiliations: Department of Dermatology, The Third People's Hospital of Hangzhou, Hangzhou, Zhejiang 310009, P.R. China
    Copyright: © Sun et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 858-866
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    Published online on: December 11, 2019
       https://doi.org/10.3892/mmr.2019.10878
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Abstract

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.
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Copy and paste a formatted citation
Spandidos Publications style
Sun X, Wang T, Huang B, Ruan G and Xu A: ΜicroRNA‑421 participates in vitiligo development through regulating human melanocyte survival by targeting receptor‑interacting serine/threonine kinase 1. Mol Med Rep 21: 858-866, 2020.
APA
Sun, X., Wang, T., Huang, B., Ruan, G., & Xu, A. (2020). ΜicroRNA‑421 participates in vitiligo development through regulating human melanocyte survival by targeting receptor‑interacting serine/threonine kinase 1. Molecular Medicine Reports, 21, 858-866. https://doi.org/10.3892/mmr.2019.10878
MLA
Sun, X., Wang, T., Huang, B., Ruan, G., Xu, A."ΜicroRNA‑421 participates in vitiligo development through regulating human melanocyte survival by targeting receptor‑interacting serine/threonine kinase 1". Molecular Medicine Reports 21.2 (2020): 858-866.
Chicago
Sun, X., Wang, T., Huang, B., Ruan, G., Xu, A."ΜicroRNA‑421 participates in vitiligo development through regulating human melanocyte survival by targeting receptor‑interacting serine/threonine kinase 1". Molecular Medicine Reports 21, no. 2 (2020): 858-866. https://doi.org/10.3892/mmr.2019.10878
Copy and paste a formatted citation
x
Spandidos Publications style
Sun X, Wang T, Huang B, Ruan G and Xu A: ΜicroRNA‑421 participates in vitiligo development through regulating human melanocyte survival by targeting receptor‑interacting serine/threonine kinase 1. Mol Med Rep 21: 858-866, 2020.
APA
Sun, X., Wang, T., Huang, B., Ruan, G., & Xu, A. (2020). ΜicroRNA‑421 participates in vitiligo development through regulating human melanocyte survival by targeting receptor‑interacting serine/threonine kinase 1. Molecular Medicine Reports, 21, 858-866. https://doi.org/10.3892/mmr.2019.10878
MLA
Sun, X., Wang, T., Huang, B., Ruan, G., Xu, A."ΜicroRNA‑421 participates in vitiligo development through regulating human melanocyte survival by targeting receptor‑interacting serine/threonine kinase 1". Molecular Medicine Reports 21.2 (2020): 858-866.
Chicago
Sun, X., Wang, T., Huang, B., Ruan, G., Xu, A."ΜicroRNA‑421 participates in vitiligo development through regulating human melanocyte survival by targeting receptor‑interacting serine/threonine kinase 1". Molecular Medicine Reports 21, no. 2 (2020): 858-866. https://doi.org/10.3892/mmr.2019.10878
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