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Chronic Stress-Induced Gene Changes In Vitro and In Vivo: Potential Biomarkers Associated With Depression and Cancer Based on circRNA- and lncRNA-Associated ceRNA Networks
Circular RNAs (circRNAs) and long noncoding RNAs (lncRNAs) have been considered as biomarkers or regulators in many diseases. However, the exact role of circRNA- or lncRNA-mediated competing endogenous RNA (ceRNA) networks in the modulation of depression pathogenesis-relevant processes is not clear....
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8507324/ https://www.ncbi.nlm.nih.gov/pubmed/34650925 http://dx.doi.org/10.3389/fonc.2021.744251 |
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author | Zhou, Ting Li, Mingming Xiao, Zhijun Cai, Jian Zhao, Weiwei Duan, Jingjing Yang, Zhen Guo, Zhijun Chen, Yitian Cai, Weijia Huang, Piaopiao He, Chaoyong Xu, Feng |
author_facet | Zhou, Ting Li, Mingming Xiao, Zhijun Cai, Jian Zhao, Weiwei Duan, Jingjing Yang, Zhen Guo, Zhijun Chen, Yitian Cai, Weijia Huang, Piaopiao He, Chaoyong Xu, Feng |
author_sort | Zhou, Ting |
collection | PubMed |
description | Circular RNAs (circRNAs) and long noncoding RNAs (lncRNAs) have been considered as biomarkers or regulators in many diseases. However, the exact role of circRNA- or lncRNA-mediated competing endogenous RNA (ceRNA) networks in the modulation of depression pathogenesis-relevant processes is not clear. In this study, we profiled whole transcriptome in depression patients’ blood samples via microarray analysis. As a result, a total of 340 circRNAs, 398 lncRNAs, 206 miRNAs, and 92 mRNAs were differentially expressed between the depression and control groups. Then, we constructed ceRNA networks according to the differentially expressed genes (DEGs). Using bioinformatics analysis, 89 pairs of circRNA-ceRNA and 49 pairs of lncRNA-ceRNA networks were obtained. Since depression is a broad and heterogeneous condition that is known as promoter for many chronic diseases including cancer, so we further dug out 28 circRNAs, 61 lncRNAs, 26 miRNAs, and 29 mRNAs that are associated with cancer. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that the DEGs were significantly enriched in cancer-related signaling pathways such as MAPK, Wnt, IL-17, Ras, and PI3K-Akt. Genes involved in the above pathways such as S100A9, GATA2, SRFP5, SLC45A3, NTRK1, FRZB, has_circ_0014221, has_circ_0014220, and has_circ_0087100 were dysregulated in various cancer cell lines by stress hormones induced. HDC, GATA2, SLC45A3, and NTRK1 were downregulated in tumor-bearing mice subjected to chronic unpredictable mild stress (CUMS). LncRNA-mediated ceRNA network validation showed that overexpression of miR-4530 declined HDC level. Our findings highlight the potential circRNA- and lncRNA-mediated ceRNA regulatory mechanisms in the pathogenesis of depression and as potential biomarkers in depression cancer comorbidity through the pathways of IL-17 or histidine metabolism. |
format | Online Article Text |
id | pubmed-8507324 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-85073242021-10-13 Chronic Stress-Induced Gene Changes In Vitro and In Vivo: Potential Biomarkers Associated With Depression and Cancer Based on circRNA- and lncRNA-Associated ceRNA Networks Zhou, Ting Li, Mingming Xiao, Zhijun Cai, Jian Zhao, Weiwei Duan, Jingjing Yang, Zhen Guo, Zhijun Chen, Yitian Cai, Weijia Huang, Piaopiao He, Chaoyong Xu, Feng Front Oncol Oncology Circular RNAs (circRNAs) and long noncoding RNAs (lncRNAs) have been considered as biomarkers or regulators in many diseases. However, the exact role of circRNA- or lncRNA-mediated competing endogenous RNA (ceRNA) networks in the modulation of depression pathogenesis-relevant processes is not clear. In this study, we profiled whole transcriptome in depression patients’ blood samples via microarray analysis. As a result, a total of 340 circRNAs, 398 lncRNAs, 206 miRNAs, and 92 mRNAs were differentially expressed between the depression and control groups. Then, we constructed ceRNA networks according to the differentially expressed genes (DEGs). Using bioinformatics analysis, 89 pairs of circRNA-ceRNA and 49 pairs of lncRNA-ceRNA networks were obtained. Since depression is a broad and heterogeneous condition that is known as promoter for many chronic diseases including cancer, so we further dug out 28 circRNAs, 61 lncRNAs, 26 miRNAs, and 29 mRNAs that are associated with cancer. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that the DEGs were significantly enriched in cancer-related signaling pathways such as MAPK, Wnt, IL-17, Ras, and PI3K-Akt. Genes involved in the above pathways such as S100A9, GATA2, SRFP5, SLC45A3, NTRK1, FRZB, has_circ_0014221, has_circ_0014220, and has_circ_0087100 were dysregulated in various cancer cell lines by stress hormones induced. HDC, GATA2, SLC45A3, and NTRK1 were downregulated in tumor-bearing mice subjected to chronic unpredictable mild stress (CUMS). LncRNA-mediated ceRNA network validation showed that overexpression of miR-4530 declined HDC level. Our findings highlight the potential circRNA- and lncRNA-mediated ceRNA regulatory mechanisms in the pathogenesis of depression and as potential biomarkers in depression cancer comorbidity through the pathways of IL-17 or histidine metabolism. Frontiers Media S.A. 2021-09-28 /pmc/articles/PMC8507324/ /pubmed/34650925 http://dx.doi.org/10.3389/fonc.2021.744251 Text en Copyright © 2021 Zhou, Li, Xiao, Cai, Zhao, Duan, Yang, Guo, Chen, Cai, Huang, He and Xu https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Zhou, Ting Li, Mingming Xiao, Zhijun Cai, Jian Zhao, Weiwei Duan, Jingjing Yang, Zhen Guo, Zhijun Chen, Yitian Cai, Weijia Huang, Piaopiao He, Chaoyong Xu, Feng Chronic Stress-Induced Gene Changes In Vitro and In Vivo: Potential Biomarkers Associated With Depression and Cancer Based on circRNA- and lncRNA-Associated ceRNA Networks |
title | Chronic Stress-Induced Gene Changes In Vitro and In Vivo: Potential Biomarkers Associated With Depression and Cancer Based on circRNA- and lncRNA-Associated ceRNA Networks |
title_full | Chronic Stress-Induced Gene Changes In Vitro and In Vivo: Potential Biomarkers Associated With Depression and Cancer Based on circRNA- and lncRNA-Associated ceRNA Networks |
title_fullStr | Chronic Stress-Induced Gene Changes In Vitro and In Vivo: Potential Biomarkers Associated With Depression and Cancer Based on circRNA- and lncRNA-Associated ceRNA Networks |
title_full_unstemmed | Chronic Stress-Induced Gene Changes In Vitro and In Vivo: Potential Biomarkers Associated With Depression and Cancer Based on circRNA- and lncRNA-Associated ceRNA Networks |
title_short | Chronic Stress-Induced Gene Changes In Vitro and In Vivo: Potential Biomarkers Associated With Depression and Cancer Based on circRNA- and lncRNA-Associated ceRNA Networks |
title_sort | chronic stress-induced gene changes in vitro and in vivo: potential biomarkers associated with depression and cancer based on circrna- and lncrna-associated cerna networks |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8507324/ https://www.ncbi.nlm.nih.gov/pubmed/34650925 http://dx.doi.org/10.3389/fonc.2021.744251 |
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