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N6-Methyladenosine modification (m6A) of circRNA-ZNF638 contributes to the induced activation of SHF stem cells through miR-361-5p/Wnt5a axis in cashmere goats

  • Ronghuan Yin (College of Animal Science and Veterinary Medicine, Shenyang Agricultural University) ;
  • Ronglan Yin (Research Academy of Animal Husbandry and Veterinary Medicine Sciences of Jilin Province) ;
  • Man Bai (College of Animal Science and Veterinary Medicine, Shenyang Agricultural University) ;
  • Yixing Fan (College of Animal Science and Veterinary Medicine, Shenyang Agricultural University) ;
  • Zeying Wang (College of Animal Science and Veterinary Medicine, Shenyang Agricultural University) ;
  • Yubo Zhu (College of Animal Science and Veterinary Medicine, Shenyang Agricultural University) ;
  • Qi Zhang (College of Animal Science and Veterinary Medicine, Shenyang Agricultural University) ;
  • Taiyu Hui (College of Animal Science and Veterinary Medicine, Shenyang Agricultural University) ;
  • Jincheng Shen (College of Animal Science and Veterinary Medicine, Shenyang Agricultural University) ;
  • Siyu Feng (College of Animal Science and Veterinary Medicine, Shenyang Agricultural University) ;
  • Wenlin Bai (College of Animal Science and Veterinary Medicine, Shenyang Agricultural University)
  • Received : 2022.05.27
  • Accepted : 2022.10.01
  • Published : 2023.04.01

Abstract

Objective: The objective of this study was to investigate the effects of N6-Methyladenosine modification-circRNA-zinc finger protein 638 (m6A-circRNA-ZNF638) on the induced activation of secondary hair follicle (SHF) stem cells with its potential mechanisms in cashmere goats. Methods: The m6A modification of ZNF638 was analyzed using methylation immunoprecipitation with real-time quantitative polymerase chain reaction technique in SHF stem cells. The effects of circRNA-ZNF638 on the induced activation of SHF stem cells in m6A dependence were evaluated through the overexpression of circRNA-ZNF638/its m6A-deficient mutants in circRNA-ZNF638 knockdown SHF stem cells. The competitive binding of miR-361-5p to circRNA-ZNF638/Wnt5a 3'- untranslated region was analyzed through Dual-luciferase reporter assay. Results: The m6A-circRNA-ZNF638 had significantly higher transcription at anagen SHF bulge of cashmere goats compared with that at telogen, as well as it positively regulated the induced activation of SHF-stem cells in cashmere goats. Mechanismly, m6A-circRNA-ZNF638 sponged miR-361-5p to heighten the transcriptional expression of Wnt5a gene in SHF-stem cells. We further demonstrated that the internal m6A modification within circRNA-ZNF638 is required for mediating the miR-361-5p/Wnt5a pathway to regulate the induced activation of SHF stem cells through an introducing of m6A-deficient mutant of circRNA-ZNF638. Conclusion: The circRNA-ZNF638 contributes the proper induced activation of SHF-stem cells in cashmere goats in m6A-dependent manner through miR-361-5p/Wnt5a axis.

Keywords

Acknowledgement

The authors thank Shiquan Wang for help in collecting skin samples from the goats.

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