Inhibition of miRNA-365-2-5p Targeting SIRT1 Regulates Functions of Keratinocytes to Enhance Wound Healing

Abstract

The development of drugs to accelerate wound healing is an important area of clinical research. Recent advancements have highlighted the prospects of microRNAs as therapeutic targets for various disorders, although their involvement in mice wound healing remains unclear. Peptides have been proved to be unique and irreplaceable molecules in the elucidation of competing endogenous RNAs mechanisms (ceRNA) involved with skin wound healing. In the present work, Cy_RL-QN15, a peptide characterized by its minimal length and maximal wound healing efficacy, was applied as a probe to explore the ceRNA mechanism in regard to accelerated wound healing. Results showed that the use of Cy_RL-QN15 significantly reduced the expression of miRNA-365-2-5p at the wound in mice. In mouse keratinocytes, miRNA-365-2-5p inhibition increased SIRT1 and FOXO1 protein expression and decreased STAT2 protein expression, promoting cell proliferation, migration, and reducing inflammatory factors. Similarly, inhibiting miRNA-365-2-5p at mouse wounds promoted Full-thickness injured skin wounds healing, increased SIRT1 and FOXO1 protein expression, decreased STAT2 protein expression, and reduced inflammatory factors. Overall, these findings demonstrate that miRNA-365-2-5p serves a crucial function in the biological processes underlying cutaneous wound healing in mice, offering a novel target for future therapeutic interventions in wound healing.