We previously reported that hsa-miR-520d-5p is functionally involved in the induction of the epithelial–mesenchymal transition and stemness-mediated processes in normal cells and cancer cells, respectively. On the basis of the synergistic effect of p53 upregulation and demethylation induced by 520d-5p, the current study investigated the effect of this miRNA on apoptotic induction by ultraviolet B (UVB) light in normal human dermal fibroblast (NHDF) cells. 520d-5p was lentivirally transfected into NHDF cells either before or after a lethal dose of UVB irradiation (302 nm) to assess its preventive or therapeutic effects, respectively. The methylation level, gene expression, production of type I collagen and cell cycle distribution were estimated in UV-irradiated cells. NHDF cells transfected with 520d-5p prior to UVB irradiation had apoptotic characteristics, and the transfection exerted no preventive effects. However, transfection with 520d-5p into NHDF cells after UVB exposure resulted in the induction of reprogramming in damaged fibroblasts, the survival of CD105-positive cells, an extended cell lifespan and prevention of cellular damage or malfunction; these outcomes were similar to the effects observed in 520d-5p-transfected NHDF cells (520d/NHDF). The gene expression of c-Abl (Abelson murine leukemia viral oncogene homolog 1), ATR (ataxia telangiectasia and Rad3-related protein), and BRCA1 (breast cancer susceptibility gene I) in transfectants was transcriptionally upregulated in order. These mechanistic findings indicate that ATR-dependent DNA damage repair was activated under this stressor. In conclusion, 520d-5p exerted a therapeutic effect on cells damaged by UVB and restored them to a normal senescent state following functional restoration via survival of CD105-positive cells through c-Abl-ATR-BRCA1 pathway activation, p53 upregulation, and demethylation.

我们以前曾报道过，hsa-miR-520d-5p在功能上分别参与正常细胞和癌细胞中上皮-间质转化和干性介导的过程的诱导。基于520d-5p诱导的p53上调和去甲基化的协同作用，当前研究研究了该miRNA对正常人真皮成纤维细胞（NHDF）细胞中紫外线B（UVB）诱导凋亡的影响。在致死剂量的UVB照射（302 nm）之前或之后，将520d-5p慢病毒转染到NHDF细胞中，以分别评估其预防或治疗效果。在紫外线照射的细胞中估计甲基化水平，基因表达，I型胶原蛋白的产生和细胞周期分布。在紫外线照射前用520d-5p转染的NHDF细胞具有凋亡特性，并且转染没有任何预防作用。然而，在暴露于紫外线后，将520d-5p转染到NHDF细胞中会导致受损的成纤维细胞重新编程，CD105阳性细胞的存活，延长的细胞寿命并防止细胞损伤或功能障碍；这些结果类似于在520d-5p转染的NHDF细胞（520d / NHDF）中观察到的效果。c-Abl（阿贝尔森鼠白血病病毒致癌基因同源物1），ATR（共济失调毛细血管扩张和Rad3相关蛋白）和BRCA1（乳腺癌易感基因I）的基因表达在转录中的表达顺序受到了上调。这些机制的发现表明，在该应激源下激活了依赖ATR的DNA损伤修复。