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Expression profiling and functional analysis of circular RNAs in vitro model of intermittent hypoxia-induced liver injury
Intermittent hypoxia (IH) is a prominent feature of obstructive sleep apnea (OSA) which is increasingly recognized as a key risk factor for liver injury. Circular RNAs (circRNAs) has been suggested to act as a regulator of multiple biological processes. However, there is no study evaluating circRNAs...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9515621/ https://www.ncbi.nlm.nih.gov/pubmed/36187780 http://dx.doi.org/10.3389/fphys.2022.972407 |
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author | Chen, Li-Da Huang, Jie-Feng Lin, Xue-Jun Huang, Ya-Ping Xu, Qiao-Zhen Chen, Gong-Ping Lin, Qi-Chang |
author_facet | Chen, Li-Da Huang, Jie-Feng Lin, Xue-Jun Huang, Ya-Ping Xu, Qiao-Zhen Chen, Gong-Ping Lin, Qi-Chang |
author_sort | Chen, Li-Da |
collection | PubMed |
description | Intermittent hypoxia (IH) is a prominent feature of obstructive sleep apnea (OSA) which is increasingly recognized as a key risk factor for liver injury. Circular RNAs (circRNAs) has been suggested to act as a regulator of multiple biological processes. However, there is no study evaluating circRNAs alterations and potential role of circRNAs in OSA-related liver injury. The present study aimed to investigate circRNA expression profiles in vitro model of IH-induced liver injury, as well as potential functional characterization of the differentially expressed circRNAs (DE circRNAs). BRL-3A cells were exposed to IH or normoxia. Cell apoptosis and cell viability were evaluated using flow cytometry and cell counting kit-8, respectively. The expression profile of circRNAs was depicted by circRNA sequencing. The selected circRNAs were verified by quantitative real-time PCR (qRT-PCR). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) analyses were employed to predict DE circRNAs functions. The circRNA-miRNA-mRNA regulatory network was constructed. IH treatment caused cell injury in BRL-3A cells. 98 circRNAs were identified as being dysregulated in IH-treated BRL-3A cells. Among them, 58 were up-regulated and 40 were down-regulated. Go and KEGG analyses suggested that the DE circRNAs were predominantly enriched in the biological process such as positive regulation of NF−kappaB transcription factor activity and pathways such as circadian entrainment, Wnt signaling pathway, MAPK signaling pathway, and protein export. 3 up-regulated circRNAs and 3 down-regulated circRNAs with high number of back-splicing sites were chosen for qRT-PCR validation and were consistent with the sequencing data. CircRNA1056 and circRNA805 were predicted to interact with microRNAs that might thereby regulate downstream genes. The study characterized a profile of dysregulated circRNAs in IH-induced BRL-3A cell injury. DE circRNAs may play vital roles in the pathophysiology of IH-induced liver injury. Our findings provide preliminary support for further research in mechanisms and a new theory for the pathogenesis of OSA-related liver injury. |
format | Online Article Text |
id | pubmed-9515621 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-95156212022-09-29 Expression profiling and functional analysis of circular RNAs in vitro model of intermittent hypoxia-induced liver injury Chen, Li-Da Huang, Jie-Feng Lin, Xue-Jun Huang, Ya-Ping Xu, Qiao-Zhen Chen, Gong-Ping Lin, Qi-Chang Front Physiol Physiology Intermittent hypoxia (IH) is a prominent feature of obstructive sleep apnea (OSA) which is increasingly recognized as a key risk factor for liver injury. Circular RNAs (circRNAs) has been suggested to act as a regulator of multiple biological processes. However, there is no study evaluating circRNAs alterations and potential role of circRNAs in OSA-related liver injury. The present study aimed to investigate circRNA expression profiles in vitro model of IH-induced liver injury, as well as potential functional characterization of the differentially expressed circRNAs (DE circRNAs). BRL-3A cells were exposed to IH or normoxia. Cell apoptosis and cell viability were evaluated using flow cytometry and cell counting kit-8, respectively. The expression profile of circRNAs was depicted by circRNA sequencing. The selected circRNAs were verified by quantitative real-time PCR (qRT-PCR). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) analyses were employed to predict DE circRNAs functions. The circRNA-miRNA-mRNA regulatory network was constructed. IH treatment caused cell injury in BRL-3A cells. 98 circRNAs were identified as being dysregulated in IH-treated BRL-3A cells. Among them, 58 were up-regulated and 40 were down-regulated. Go and KEGG analyses suggested that the DE circRNAs were predominantly enriched in the biological process such as positive regulation of NF−kappaB transcription factor activity and pathways such as circadian entrainment, Wnt signaling pathway, MAPK signaling pathway, and protein export. 3 up-regulated circRNAs and 3 down-regulated circRNAs with high number of back-splicing sites were chosen for qRT-PCR validation and were consistent with the sequencing data. CircRNA1056 and circRNA805 were predicted to interact with microRNAs that might thereby regulate downstream genes. The study characterized a profile of dysregulated circRNAs in IH-induced BRL-3A cell injury. DE circRNAs may play vital roles in the pathophysiology of IH-induced liver injury. Our findings provide preliminary support for further research in mechanisms and a new theory for the pathogenesis of OSA-related liver injury. Frontiers Media S.A. 2022-09-14 /pmc/articles/PMC9515621/ /pubmed/36187780 http://dx.doi.org/10.3389/fphys.2022.972407 Text en Copyright © 2022 Chen, Huang, Lin, Huang, Xu, Chen and Lin. 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 | Physiology Chen, Li-Da Huang, Jie-Feng Lin, Xue-Jun Huang, Ya-Ping Xu, Qiao-Zhen Chen, Gong-Ping Lin, Qi-Chang Expression profiling and functional analysis of circular RNAs in vitro model of intermittent hypoxia-induced liver injury |
title | Expression profiling and functional analysis of circular RNAs in vitro model of intermittent hypoxia-induced liver injury |
title_full | Expression profiling and functional analysis of circular RNAs in vitro model of intermittent hypoxia-induced liver injury |
title_fullStr | Expression profiling and functional analysis of circular RNAs in vitro model of intermittent hypoxia-induced liver injury |
title_full_unstemmed | Expression profiling and functional analysis of circular RNAs in vitro model of intermittent hypoxia-induced liver injury |
title_short | Expression profiling and functional analysis of circular RNAs in vitro model of intermittent hypoxia-induced liver injury |
title_sort | expression profiling and functional analysis of circular rnas in vitro model of intermittent hypoxia-induced liver injury |
topic | Physiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9515621/ https://www.ncbi.nlm.nih.gov/pubmed/36187780 http://dx.doi.org/10.3389/fphys.2022.972407 |
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