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Transcriptome Sequencing Reveals Tgf-β-Mediated Noncoding RNA Regulatory Mechanisms Involved in DNA Damage in the 661W Photoreceptor Cell Line

Transforming growth factor β (Tgf-β), a pleiotropic cytokine, can enhance DNA repair in various cells, including cancer cells and neurons. The noncoding regulatory system plays an important role in Tgf-β-mediated biological activities, whereas few studies have explored its role in DNA damage and rep...

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Autores principales: Huang, Yuke, Chen, Xi, Jiang, Zhigao, Luo, Qian, Wan, Linxi, Hou, Xiangtao, Yu, Keming, Zhuang, Jing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9691224/
https://www.ncbi.nlm.nih.gov/pubmed/36421815
http://dx.doi.org/10.3390/genes13112140
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author Huang, Yuke
Chen, Xi
Jiang, Zhigao
Luo, Qian
Wan, Linxi
Hou, Xiangtao
Yu, Keming
Zhuang, Jing
author_facet Huang, Yuke
Chen, Xi
Jiang, Zhigao
Luo, Qian
Wan, Linxi
Hou, Xiangtao
Yu, Keming
Zhuang, Jing
author_sort Huang, Yuke
collection PubMed
description Transforming growth factor β (Tgf-β), a pleiotropic cytokine, can enhance DNA repair in various cells, including cancer cells and neurons. The noncoding regulatory system plays an important role in Tgf-β-mediated biological activities, whereas few studies have explored its role in DNA damage and repair. In this study, we suggested that Tgf-β improved while its inhibitor LSKL impaired DNA repair and cell viability in UV-irradiated 661W cells. Moreover, RNA-seq was carried out, and a total of 106 differentially expressed (DE)-mRNAs and 7 DE-lncRNAs were identified between UV/LSKL and UV/ctrl 661W cells. Gene ontology and Reactome analysis confirmed that the DE-mRNAs were enriched in multiple DNA damaged- and repair-related biological functions and pathways. We then constructed a ceRNA network that included 3 lncRNAs, 19 miRNAs, and 29 mRNAs with a bioinformatics prediction. Through RT-qPCR and further functional verification, 2 Tgf-β-mediated ceRNA axes (Gm20559-miR-361-5p-Oas2/Gbp7) were further identified. Gm20559 knockout or miR-361-5p mimics markedly impaired DNA repair and cell viability in UV-irradiated 661W cells, which confirms the bioinformatics results. In summary, this study revealed that Tgf-β could reduce DNA damage in 661W cells, provided a Tgf-β-associated ceRNA network for DNA damage and repair, and suggested that the molecular signatures may be useful candidates as targets of treatment for photoreceptor pathology.
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spelling pubmed-96912242022-11-25 Transcriptome Sequencing Reveals Tgf-β-Mediated Noncoding RNA Regulatory Mechanisms Involved in DNA Damage in the 661W Photoreceptor Cell Line Huang, Yuke Chen, Xi Jiang, Zhigao Luo, Qian Wan, Linxi Hou, Xiangtao Yu, Keming Zhuang, Jing Genes (Basel) Article Transforming growth factor β (Tgf-β), a pleiotropic cytokine, can enhance DNA repair in various cells, including cancer cells and neurons. The noncoding regulatory system plays an important role in Tgf-β-mediated biological activities, whereas few studies have explored its role in DNA damage and repair. In this study, we suggested that Tgf-β improved while its inhibitor LSKL impaired DNA repair and cell viability in UV-irradiated 661W cells. Moreover, RNA-seq was carried out, and a total of 106 differentially expressed (DE)-mRNAs and 7 DE-lncRNAs were identified between UV/LSKL and UV/ctrl 661W cells. Gene ontology and Reactome analysis confirmed that the DE-mRNAs were enriched in multiple DNA damaged- and repair-related biological functions and pathways. We then constructed a ceRNA network that included 3 lncRNAs, 19 miRNAs, and 29 mRNAs with a bioinformatics prediction. Through RT-qPCR and further functional verification, 2 Tgf-β-mediated ceRNA axes (Gm20559-miR-361-5p-Oas2/Gbp7) were further identified. Gm20559 knockout or miR-361-5p mimics markedly impaired DNA repair and cell viability in UV-irradiated 661W cells, which confirms the bioinformatics results. In summary, this study revealed that Tgf-β could reduce DNA damage in 661W cells, provided a Tgf-β-associated ceRNA network for DNA damage and repair, and suggested that the molecular signatures may be useful candidates as targets of treatment for photoreceptor pathology. MDPI 2022-11-17 /pmc/articles/PMC9691224/ /pubmed/36421815 http://dx.doi.org/10.3390/genes13112140 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Huang, Yuke
Chen, Xi
Jiang, Zhigao
Luo, Qian
Wan, Linxi
Hou, Xiangtao
Yu, Keming
Zhuang, Jing
Transcriptome Sequencing Reveals Tgf-β-Mediated Noncoding RNA Regulatory Mechanisms Involved in DNA Damage in the 661W Photoreceptor Cell Line
title Transcriptome Sequencing Reveals Tgf-β-Mediated Noncoding RNA Regulatory Mechanisms Involved in DNA Damage in the 661W Photoreceptor Cell Line
title_full Transcriptome Sequencing Reveals Tgf-β-Mediated Noncoding RNA Regulatory Mechanisms Involved in DNA Damage in the 661W Photoreceptor Cell Line
title_fullStr Transcriptome Sequencing Reveals Tgf-β-Mediated Noncoding RNA Regulatory Mechanisms Involved in DNA Damage in the 661W Photoreceptor Cell Line
title_full_unstemmed Transcriptome Sequencing Reveals Tgf-β-Mediated Noncoding RNA Regulatory Mechanisms Involved in DNA Damage in the 661W Photoreceptor Cell Line
title_short Transcriptome Sequencing Reveals Tgf-β-Mediated Noncoding RNA Regulatory Mechanisms Involved in DNA Damage in the 661W Photoreceptor Cell Line
title_sort transcriptome sequencing reveals tgf-β-mediated noncoding rna regulatory mechanisms involved in dna damage in the 661w photoreceptor cell line
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9691224/
https://www.ncbi.nlm.nih.gov/pubmed/36421815
http://dx.doi.org/10.3390/genes13112140
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