Hsa-miR-520d-5p promotes survival in human dermal fibroblasts exposed to a lethal dose of UV irradiation

Abstract

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.

<p>Induction of Autophagy by Baicalin Through the AMPK-mTOR Pathway Protects Human Skin Fibroblasts from Ultraviolet B Radiation-Induced Apoptosis</p>

“…13 In the present study, we found that baicalin increased cell viability ( Figure 1A) and suppressed apoptosis (Figure 2A and B) of human fibroblast cells induced by UVB at 600 J/m 2 , the dose level high enough to caused fibroblast cells to undergo apoptosis. 39,40 UVB radiation is capable of activating several apoptotic pathways by inducing DNA damage and activating tumor suppressor gene p53. 24 As UVB radiation activates p53 signaling pathway, the downstream proapoptotic Bax is upregulated and anti-apoptotic Bcl-2 is suppressed, leading cell arrest and apoptosis.…”

Potential Biological Molecules and Immune Cell for Rheumatoid Arthritis Synovial Lesions

“…We also found two key miRNAs (miR-520d-5p and miR-139-5p). Previous studies have found that miR-520d-5p can promote the survival of human dermal broblasts exposed to a lethal dose of ultraviolet radiation (20). Undifferentiated collagen-bound miR-520d-5p has anti-tumor effect on undifferentiated cancer cells in a mouse xenograft model (21).…”

MiR-520d-5p modulates chondrogenesis and chondrocyte metabolism through targeting HDAC1

“…Many studies so far demonstrated that miR-520d-5p participates in diverse cellular processes. In human dermal fibroblast (NHDF) cells, miR-520d-5p repairs damages induced by ultraviolet B and restore damaged cells to normal senescent state through the survival of CD105-positive cells via c-Abl-ATR-BRCA1/p53 signaling pathways [ 37 ]. Given its anti-tumor effect, miR-520d-5p suppresses human glioma cell proliferation through targeting PTTG1 [ 38 ] and inhibits tumor metastasis and growth by binding to CTHRC1 in colorectal cancer [ 39 ].…”