MiR-23a-27a-24表达簇在急性中波紫外线辐射所致CPDs清除及凋亡过程中的作用和机制研究

Ultraviolet (UV) light is electromagnetic radiation, it is accepted that excess UVB irradiation is a major risk factor for skin cancers. Although UVB absorption can damage various skin cell components, carcinogenesis is primarily due to photolesions formed in DNA, which are predominantly cyclobutane pyrimidine dimers (CPDs) . Recently, our research group assessed the effects of UVB irradiation on miRNA expression in normal human keratinocytes. The miR-23a~27a~24 cluster, which has been reported to play a role in anti-tumorigenic pathways, DNA repair, and apoptosis, was found to be up-regulated 4 and 24 hours post-irradiation . MiR-23a protects against UVB-induced injury to HaCaT cells via its regulation of potential target genes, Caspase-7, STK4, and TOP1. Whether the UVB-regulated miRNAs, including miR-27a, can influence the response to UVB-induced cell damage, such as through CPDs removal, apoptosis is explored in the present study, the relationship between miR-23a and miR-27a is also included in our research. The results of this investigation provide a model to understand the molecular regulation of miR-23a~27a~24 cluster in UVB-induced cellular damage.

中波紫外线（UVB）能够直接或间接作用于皮肤细胞的DNA，导致DNA损伤，引起光源性皮肤损伤、光老化，甚至多种皮肤肿瘤。核酸类抗光损伤产品已有研究，但通过miRNA靶点进行UVB辐射损伤的防护及治疗尚属空白。MiR-23a-27a-24表达簇上的miR-23a、miR-27a在UVB辐射后表达水平都发生了显著的变化，前期研究证实miR-23a可通过对靶基因Caspase-7、STK4以及TOP1的调控发挥光损伤保护作用，但miR-27a在UVB急性光损伤中的作用及miR-23a及miR-27a之间的相互作用尚未明确。本项目拟通过研究UVB急性光损伤模型中miR-27a的作用、作用机制以及其与miR-23a之间的相互作用，来进一步揭示miR-23a-27a-24表达簇在UVB急性光损伤中的功能，以进一步深化了解光源性皮肤损伤中的miRNA调控机制，为预防及治疗光损伤寻找有效靶点。

中波紫外线（UVB）能够直接或间接作用于皮肤细胞的DNA，导致DNA损伤，引起光源性皮肤损伤、光老化，甚至多种皮肤肿瘤。核酸类抗光损伤产品已有研究，但通过miRNA靶点进行UVB辐射损伤的防护及治疗尚属空白。本研究证实了MiR-23a-27a-24表达簇上的miR-23a、miR-27a在UVB辐射后表达水平都发生了显著的变化，并证实miR-27a可通过对靶基因APAF-1的调控发挥光损伤保护作用，与同一表达簇上的miR-23a在UVB辐射后发挥协同保护作用。具体表现在miR-27a可增强UVB辐射所致急性光损伤后细胞及动物模型中CPDs的清除及减少辐射所致的细胞凋亡，其作用主要通过对靶基因APAF-1的调控来实现，并在动物模型中验证了这些结果。通过对miR-23a、miR-27a表达的共干扰法证实在MiR-23a-27a-24表达簇上主要由miR-23a、miR-27a发挥光保护作用，两者通过对APAF-1的调控发挥协同作用。. 总之，本研究进一步深化了解了光源性皮肤损伤中的miRNA调控机制，为预防及治疗光损伤寻找了一个潜在的有效靶点。