TY - JOUR TI - MicroRNA-200b/c-3p regulate epithelial plasticity and inhibit cutaneous wound healing by modulating TGF-β-mediated RAC1 signaling AU - Tang, Huiyi AU - Wang, Xueer AU - Zhang, Min AU - Yan, Yuan AU - Huang, Simin AU - Ji, Jiahao AU - Xu, Jinfu AU - Zhang, Yijia AU - Cai, Yongjie AU - Yang, Bobo AU - Lan, Wenqi AU - Huang, Mianbo AU - Zhang, Lin T2 - Cell Death & Disease AB - Cutaneous wound healing is pivotal for human skin to regain barrier function against pathogens. MicroRNAs (miRNAs) have been found to play regulatory roles in wound healing. However, the mechanism of miRNA regulation remains largely unknown. In this study, we focused on microRNA-200b/c-3p (miR-200b/c-3p) whose expression was abundant in intact epidermis, but dramatically decreased in skin wounds. In silico prediction identified RAC1 as a potential miR-200b/c-3p target. Luciferase reporter assay confirmed that miR-200b/c-p repressed RAC1 by direct targeting to its mRNA 3′UTR. Consistently, miR-200b/c-3p expression was discordantly related to RAC1 protein level during wound healing. Forced miR-200b/c-3p expression repressed RAC1 and inhibited keratinocyte migration as well as re-epithelialization in a mouse back skin full-thickness wound healing model. Mechanistically, miR-200b/c-3p modulated RAC1 to inhibit cell migration by repressing lamellipodia formation and intercellular adhesion dissolution in keratinocytes. Furthermore, we found that TGF-β1, which was highly expressed in skin wounds, contributed to the downregulation of miR-200b/c-3p in wound edge keratinocytes. Taken together, miR-200b/c-3p-mediated RAC1 repression inhibited keratinocyte migration to delay re-epithelialization. TGF-β1 induction attenuated miR-200b/c-3p regulation of RAC1 signaling in cutaneous wounds and the repression of miR-200b/c-3p accelerated keratinocyte migration to promote wound healing. Our data provide new insight into how miR-200b/c-3p affects keratinocyte migration and highlight the potential of miR-200b/c-3p targeting for accelerating wound healing. DA - 2020/10/29/ PY - 2020 DO - 10.1038/s41419-020-03132-2 DP - www.nature.com VL - 11 IS - 10 SP - 1 EP - 17 LA - en SN - 2041-4889 UR - https://www.nature.com/articles/s41419-020-03132-2 Y2 - 2020/10/29/22:18:56 ER -