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

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 ?-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.

SUBMITTER: Xu D

PROVIDER: S-EPMC7094206 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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

Xu Dan D Wang Yue Y Wang Jia J Qi Fei F Sun Yeqing Y

BioMed research international 20200313

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-depende ...[more]

PMID: 32258156

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Project description:The complex Drosophila larval peripheral nervous system, capable of monitoring sensory input from the external environment, includes a family of multiple dendritic (md) neurons with extensive dendritic arbors tiling the inner surface of the larval body wall. The class IV multiple dendritic (mdIV) neurons are the most complex with dendritic nerve endings forming direct intimate contacts with epithelial cells of the larval body wall. Functioning as polymodal mechanonociceptors with the ability to respond to both noxious mechanical stimulation and noxious heat, the mdIV neurons are also activated by nanomolar levels of the endogenous reactive oxygen species (ROS), H2O2. Although often associated with tissue damage related to oxidative stress, endogenous ROS have also been shown to function as signaling molecules at lower concentrations. The overall role of ROS in sensory signaling is poorly understood but the acutely sensitive response of mdIV neurons to ROS-mediated activation is consistent with a routine role in the regulation of mdIV neuronal activity. Larvae respond to short wavelength ultraviolet (UVC) light with an immediate and visual system-independent writhing and twisting of the body previously described as a nociceptive response. Molecular and cellular mechanisms mediating this response and potential relationships with ROS generation are not well understood. We have used the UVC-induced writhing response as a model for investigation of the proposed link between endogenous ROS production and mdIV neuron function in the larval body wall.Transgenic inactivation of mdIV neurons caused a strong suppression of UVC-induced writhing behavior consistent with a key role for the mdIV neurons as mediators of the behavioral response. Direct imaging of ROS-activated fluorescence showed that UVC irradiation caused a significant increase in endogenous ROS levels in the larval body wall and transgenic overexpression of antioxidant enzymes strongly suppressed the UVC-induced writhing response. Direct electrophysiological recordings demonstrated that UVC irradiation also increased neuronal activity of the mdIV neurons.Results obtained using UVC irradiation to induce ROS generation provide evidence that UVC-induced writhing behavior is mediated by endogenous production of ROS capable of activating mdIV mechanonociceptors in the larval body wall.

Dataset Information

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

Publications

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

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