The miR-93-3p/ZFP36L1/ZFX axis regulates keratinocyte proliferation and migration during skin wound healing

• Published in: Molecular therapy. Nucleic acids Vol. 23; pp. 450 - 463
• Main Authors: Feng, Xiao, Zhou, Shuangbai, Cai, Weilin, Guo, Jincai
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 05.03.2021; American Society of Gene & Cell Therapy; Elsevier
• Subjects: miR-93-3p; Original; skin wound healing; ZFP36L1; ZFX; miR-93-3p; ZFX; skin wound healing; ZFP36L1
• ISSN: 2162-2531; 2162-2531
• DOI: 10.1016/j.omtn.2020.11.017

Keratinocyte proliferation and migration are crucial steps during skin wound healing. The functional role of microRNAs (miRs) remains relatively unknown during this process. miR-93 levels have been reported to increase within 24 h of skin wound healing; however, whether miR-93-3p or miR-93-5p plays a specific role in wound healing is yet to be studied. In this study, with the use of an in vivo mouse skin wound-healing model, we demonstrate that miR-93-3p is significantly upregulated, whereas there is no change in the expression of miR-93-5p during skin wound healing. In HaCaT cells, miR-93-3p overexpression increased proliferation and migration of the cells, whereas miR-93-3p inhibition had the reverse effect. Additionally, it was evident that ZFP36L1 was a direct target of miR-93-3p in keratinocytes. Further, ZFP36L1 silencing mirrored the consequences observed during miR-93-3p overexpression on both proliferation and migration of keratinocytes. In addition, we demonstrate that zinc-finger X-linked (ZFX), as a target for ZFP36L1, is involved in the promotion of the miR-93-3p/ZFP36L1 axis in keratinocyte proliferation and migration. Ultimately, we found that mouse skin wound model treatment with anti-miR-93-3p delayed wound healing. Overall, our results show that miR-93-3p is a crucial regulator of skin wound healing that facilitates keratinocyte proliferation and migration through ZFP36L1/ZFX axis. [Display omitted] Feng et al. were the first to investigate the mechanism of miR-93-3p in skin wound healing. Their study demonstrated that upregulated miR-93-3p binds and downregulates ZFP36L1, causing upregulation of ZFX and subsequent stimulation of keratinocyte proliferation and migration by using a skin wound animal model and HaCaT cell line.