MiR-488 facilitates wound healing through CYP1B1-mediated Wnt/β-catenin signaling pathway by targeting MeCP2

Abstract Background: Diabetic wounds are difficult to heal, but its pathogenesis has not been elucidated. MicroRNAs (miRNAs) are considered to act as key roles in wound healing. In this paper, the role of miR-488 in wound healing was investigated. Methods: The mRNA and protein expressions were assessed using RT-qPCR and western blot. The gene methylation was measured by MSP assay. Cell proliferation, apoptosis and migration were assessed using BrdU, flow cytometer and wound healing assay, respectively. Additionally, the angiogenesis ability of HUVEC cells was analyzed using in vitro angiogenesis assay. Dual-luciferase reporter assay was adopted to analyze the interaction between miR-488 and MeCP2. Results: Here our results displayed that miR-488 and CYP1B1 expressions were markedly reduced in wound tissues of diabetic with skin defect, while MeCP2 was significantly upregulated. Function assays displayed that miR-488 promoted cell proliferation and migration as well as HUVEC cell angiogenesis through regulation of MeCP2, while inhibited the apoptosis. MiR-488 overexpression could also accelerate wound healing in vivo . MeCP2 functioned as the target of miR-488, and suppressed wound healing in vitro . We subsequently confirmed MeCP2 suppressed CYP1B1 expression via promoting its methylation status. In addition, CYP1B1 knockdown inhibited wound healing. Furthermore, MeCP2 overexpression abolished the promoting effect of miR-488 on wound healing. It was also turned out that Wnt4/β-catenin pathway was the downstream pathway of miR-488/MeCP2/CYP1B1 in regulating wound healing. Conclusion: MiR-488 is a potential therapeutic target for diabetic wound healing, since miR-488 overexpression promoted wound healing through activating CYP1B1-mediated Wnt4/β-catenin signaling pathway by targeting MeCP2.