Identifying microRNAs that drive BaP-induced pulmonary effects: Multiple patterns of mechanisms underlying activation of the toxicity pathways
MiRNAs are widely acknowledged as regulating gene expression and thus, being involved in broad biological functions, environmental responses, and the process of diseases. Epidemiology could provide exposure- or disease-relevant miRNAs, while toxicology could reveal the underlying mechanisms. Here, a...
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Elsevier
2022-12-01
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Series: | Environment International |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S0160412022005153 |
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author | Yuan Jin Qianqian Zhang Yuzhen Liu Heyuan Guan Yingqing Shou Chenlong Du Jiao Luo Kunming Zhao Chuanhai Li Lin Xu Wanli Ma Ningning Chen Yuxin Zheng Dianke Yu |
author_facet | Yuan Jin Qianqian Zhang Yuzhen Liu Heyuan Guan Yingqing Shou Chenlong Du Jiao Luo Kunming Zhao Chuanhai Li Lin Xu Wanli Ma Ningning Chen Yuxin Zheng Dianke Yu |
author_sort | Yuan Jin |
collection | DOAJ |
description | MiRNAs are widely acknowledged as regulating gene expression and thus, being involved in broad biological functions, environmental responses, and the process of diseases. Epidemiology could provide exposure- or disease-relevant miRNAs, while toxicology could reveal the underlying mechanisms. Here, a new “Bottom-up” approach was proposed to identify miRNAs that are responsible for environmental exposure-induced adverse outcomes. In our previous study, 5 key toxicity pathways were established underlying BaP-induced lung diseases; further, genes from these 5 pathways that were responsive to BaP exposure in HBE-CYP1A1 cells were identified. In this study, we identified 26 miRNA:mRNA interactions during BaP exposure through RNA-sequencing using the same HBE-CYP1A1 cells. According to the expression alteration and regulatory mechanisms, we summarized 8 action patterns of miRNA:mRNA, which led to the induction of miRNAs that predominantly regulate target genes and responsible are for the pathway perturbations (as “drivers”), and miRNAs that subordinately regulate genes during pathway perturbations (as “symptoms”). 5 corresponding miRNAs: miR-3173-5p, miR-629-3p, miR-9-5p, miR-1343-3p and miR-219a-1-3p were identified as “drivers”, and were all validated with expression alteration in lung disease patients from published studies. In conclusion, this study offers a new approach to identification of epigenetic factors that may shed light on the causation of environment-related health outcomes. |
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id | doaj.art-f87f9b12d4d7462aa187adb0ad0c6e13 |
institution | Directory Open Access Journal |
issn | 0160-4120 |
language | English |
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publishDate | 2022-12-01 |
publisher | Elsevier |
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series | Environment International |
spelling | doaj.art-f87f9b12d4d7462aa187adb0ad0c6e132022-12-22T03:48:52ZengElsevierEnvironment International0160-41202022-12-01170107588Identifying microRNAs that drive BaP-induced pulmonary effects: Multiple patterns of mechanisms underlying activation of the toxicity pathwaysYuan Jin0Qianqian Zhang1Yuzhen Liu2Heyuan Guan3Yingqing Shou4Chenlong Du5Jiao Luo6Kunming Zhao7Chuanhai Li8Lin Xu9Wanli Ma10Ningning Chen11Yuxin Zheng12Dianke Yu13School of Public Health, Qingdao University, Qingdao, ChinaSchool of Public Health, Qingdao University, Qingdao, ChinaSchool of Public Health, Qingdao University, Qingdao, ChinaSchool of Public Health, Qingdao University, Qingdao, ChinaSchool of Public Health, Qingdao University, Qingdao, ChinaSchool of Public Health, Qingdao University, Qingdao, ChinaSchool of Public Health, Qingdao University, Qingdao, ChinaSchool of Public Health, Qingdao University, Qingdao, ChinaSchool of Public Health, Qingdao University, Qingdao, ChinaSchool of Public Health, Qingdao University, Qingdao, ChinaSchool of Public Health, Qingdao University, Qingdao, ChinaSchool of Public Health, Qingdao University, Qingdao, ChinaSchool of Public Health, Qingdao University, Qingdao, ChinaCorresponding author at: School of Public Health, Qingdao University, 308 Ningxia Road, Qingdao, Shandong 266021, China.; School of Public Health, Qingdao University, Qingdao, ChinaMiRNAs are widely acknowledged as regulating gene expression and thus, being involved in broad biological functions, environmental responses, and the process of diseases. Epidemiology could provide exposure- or disease-relevant miRNAs, while toxicology could reveal the underlying mechanisms. Here, a new “Bottom-up” approach was proposed to identify miRNAs that are responsible for environmental exposure-induced adverse outcomes. In our previous study, 5 key toxicity pathways were established underlying BaP-induced lung diseases; further, genes from these 5 pathways that were responsive to BaP exposure in HBE-CYP1A1 cells were identified. In this study, we identified 26 miRNA:mRNA interactions during BaP exposure through RNA-sequencing using the same HBE-CYP1A1 cells. According to the expression alteration and regulatory mechanisms, we summarized 8 action patterns of miRNA:mRNA, which led to the induction of miRNAs that predominantly regulate target genes and responsible are for the pathway perturbations (as “drivers”), and miRNAs that subordinately regulate genes during pathway perturbations (as “symptoms”). 5 corresponding miRNAs: miR-3173-5p, miR-629-3p, miR-9-5p, miR-1343-3p and miR-219a-1-3p were identified as “drivers”, and were all validated with expression alteration in lung disease patients from published studies. In conclusion, this study offers a new approach to identification of epigenetic factors that may shed light on the causation of environment-related health outcomes.http://www.sciencedirect.com/science/article/pii/S0160412022005153miRNAToxicity pathwaysAdverse outcome pathwaysEnvironmental exposureSystems toxicologyPolycyclic aromatic hydrocarbons |
spellingShingle | Yuan Jin Qianqian Zhang Yuzhen Liu Heyuan Guan Yingqing Shou Chenlong Du Jiao Luo Kunming Zhao Chuanhai Li Lin Xu Wanli Ma Ningning Chen Yuxin Zheng Dianke Yu Identifying microRNAs that drive BaP-induced pulmonary effects: Multiple patterns of mechanisms underlying activation of the toxicity pathways Environment International miRNA Toxicity pathways Adverse outcome pathways Environmental exposure Systems toxicology Polycyclic aromatic hydrocarbons |
title | Identifying microRNAs that drive BaP-induced pulmonary effects: Multiple patterns of mechanisms underlying activation of the toxicity pathways |
title_full | Identifying microRNAs that drive BaP-induced pulmonary effects: Multiple patterns of mechanisms underlying activation of the toxicity pathways |
title_fullStr | Identifying microRNAs that drive BaP-induced pulmonary effects: Multiple patterns of mechanisms underlying activation of the toxicity pathways |
title_full_unstemmed | Identifying microRNAs that drive BaP-induced pulmonary effects: Multiple patterns of mechanisms underlying activation of the toxicity pathways |
title_short | Identifying microRNAs that drive BaP-induced pulmonary effects: Multiple patterns of mechanisms underlying activation of the toxicity pathways |
title_sort | identifying micrornas that drive bap induced pulmonary effects multiple patterns of mechanisms underlying activation of the toxicity pathways |
topic | miRNA Toxicity pathways Adverse outcome pathways Environmental exposure Systems toxicology Polycyclic aromatic hydrocarbons |
url | http://www.sciencedirect.com/science/article/pii/S0160412022005153 |
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