The Potential Regulatory Roles of lncRNAs in DNA Damage Response in Human Lymphocytes Exposed to UVC Irradiation.

Dan Xu,Fei Qi,Yeqing Sun,Yue Wang,Jia Wang

doi:10.1155/2020/8962635

Abstract

Long noncoding RNAs (lncRNAs) are a class of noncoding RNAs that modulate gene expression, thereby participating in the regulation of various cellular processes. However, it is not clear about the expression and underlying mechanism of lncRNAs in irradiation-induced DNA damage response. In the present study, we performed integrative analysis of lncRNA-mRNA expression profile in human lymphocytes irradiated with ultraviolet-C (UVC). The results showed that exposure to UVC irradiation dose-dependently increased the fluorescence intensity of γ-H2AX and induced cell death. Microarray analysis revealed that up-regulated lncRNAs were more common than down-regulated lncRNAs with the increase of radiation dose in UVC-radiated cells. Stem analysis demonstrated the relationship between lncRNA expression level and radiation dose. qPCR results confirmed that LOC338799 and its coexpressed genes such as LCE1F and ISCU showed the increase in expression levels with the increase of UVC radiation dose. We utilized Cytoscape to screen out 5 lncRNAs and 13 coexpressed genes linking to p53, which might participate in the regulation of DNA damage, cell cycle arrest, apoptosis, and cell death. These findings suggest that lncRNAs might play a role in UVC-induced DNA damage response through regulating expression of genes in p53 signaling pathway.

Highlights

Ultraviolet (UV) radiation belongs to the nonionizing part of the electromagnetic spectrum, which is subdivided into UVA, UVB (280-315 nm), and UVC (200-280 nm)
We firstly identified that the optimal radiation dose range of UVC was 4-64 J/m2, within which the percentage of dead cells was 30-70% in CD4+ T lymphocytes (CD4) cells at 24 h after UVC irradiation
The results showed that UVC radiation increased relative fluorescent intensity of γ-H2AX in a dose-dependent manner

Summary

Introduction

Ultraviolet (UV) radiation belongs to the nonionizing part of the electromagnetic spectrum, which is subdivided into UVA (wavelengths 315-400 nm), UVB (280-315 nm), and UVC (200-280 nm). UVC radiation gained more attention because UVC has direct damaging effects to cellular DNA and results in DNA single- and double-strand breaks [1, 2]. Cellular DNA has a higher absorption peak at 260 nm within the UVC band, so UVC is often used as the easiest and fastest way to produce DNA damage. UVC can induce immediate DNA damage and energy-dependent biological effects in a variety of cells. It is reported that UVC radiation-induced DNA damage provoked highly divergent responses in human skin fibroblasts exposed to low (10 J/m2) and high doses (50 J/m2) of UVC radiation [3]. Another report showed that UVC could affect the transcriptional profile in human primary cultured fibroblasts irradiated with even a low dose (0.5 or 5 J/m2) of UVC [4]

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