2. Academic Validation
  3. CircRNA_SLC8A1 alleviates hypertrophic scar progression by mediating the Nrf2-ARE pathway

CircRNA_SLC8A1 alleviates hypertrophic scar progression by mediating the Nrf2-ARE pathway

  • Mol Biol Rep. 2024 Oct 18;51(1):1067. doi: 10.1007/s11033-024-10018-5.
Yichao Jin # 1 2,  Yongjing He # 3,  Yifei Wu 1 2,  Xiaochuan Wang 1 2,  Lechun Lyu 4,  Ke Zhang 5 6,  Chunping Ao 7 8,  Liangheng Xu 9 10
Affiliations

Affiliations

  • 1 Department of Dermatology, The First People's Hospital of Yunnan Province, Kunming, Yunnan, China.
  • 2 Department of Dermatology, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, China.
  • 3 Department of Plastic Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.
  • 4 Technology Transfer Center, Kunming Medical University, Kunming, Yunnan, China.
  • 5 Department of Urinary Surgery, The First People's Hospital of Yunnan Province, Kunming, Yunnan, China.
  • 6 Department of Urinary Surgery, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, China.
  • 7 Department of Dermatology, The First People's Hospital of Yunnan Province, Kunming, Yunnan, China. aochunping11@163.com.
  • 8 Department of Dermatology, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, China. aochunping11@163.com.
  • 9 Department of Dermatology, The First People's Hospital of Yunnan Province, Kunming, Yunnan, China. heng1178@163.com.
  • 10 Department of Dermatology, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, China. heng1178@163.com.
  • # Contributed equally.
PMID: 39422836 DOI: 10.1007/s11033-024-10018-5
Abstract

Background: Hypertrophic scar (HS) is associated with cosmetic defects, mobility, and functional impairments, pruritus, and pain. Previous circRNA microarray analysis identified reduced expression of circRNA_SLC8A1 in HS tissues. Therefore, this study aims to investigate the role of circRNA_SLC8A1 in modulating the abnormal behavior of HS-derived fibroblasts (HSFs) in vitro.

Methods: RT-qPCR and FISH assays were used to assess the differential expression and localization of circRNA_SLC8A1 in normal and HS tissues. Following modulation of circRNA_SLC8A1 expression, CCK-8, flow cytometry, Transwell, and wound healing assays were employed to evaluate the effects of circRNA_SLC8A1 on the biological behaviors of HSFs. The Starbase database, dual-luciferase reporter assays, and Ago2-RIP assays were utilized to predict and validate the interaction between circRNA_SLC8A1 and downstream miRNAs.

Results: CircRNA_SLC8A1 was found to be downregulated in HS tissues and was primarily localized in the cytoplasm. Overexpression of circRNA_SLC8A1 reduced cell viability, cell invasion, wound healing, and the expression of Vimentin, N-Cadherin, Col I, and Col III, while enhancing Apoptosis and E-cadherin expression in HSFs. CircRNA_SLC8A1 activates the Nrf2-ARE pathway by competitively binding to miRNA-27a-3p. miRNA-27a-3p and Nrf2 exhibited high and low expression, respectively in HS tissues, with an inverse correlation between their levels. Overexpression of miRNA-27a-3p counteracted the effects of circRNA_SLC8A1 in HSF proliferation, Apoptosis, migration, EMT, collagen deposition, and Nrf2-ARE pathway activity.

Conclusion: CircRNA_SLC8A1 inhibits the proliferation, migration, EMT, and collagen deposition of HSF through competitive binding with miRNA-27a-3p, thereby activating the Nrf2-ARE pathway. The circRNA_SLC8A1/miRNA-27a-3p/Nrf2-ARE axis may offer a promising molecular target for HS therapy.

Keywords

Collagen deposition; Epithelial-mesenchymal transition; Hypertrophic scar; Non-coding RNA; Nrf2-ARE pathway.

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