Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Chen, Li-Da, Huang, Jie-Feng, Lin, Xue-Jun, Huang, Ya-Ping, Xu, Qiao-Zhen, Chen, Gong-Ping, Lin, Qi-Chang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
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
_version_ 1784798525643554816
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
work_keys_str_mv AT chenlida expressionprofilingandfunctionalanalysisofcircularrnasinvitromodelofintermittenthypoxiainducedliverinjury
AT huangjiefeng expressionprofilingandfunctionalanalysisofcircularrnasinvitromodelofintermittenthypoxiainducedliverinjury
AT linxuejun expressionprofilingandfunctionalanalysisofcircularrnasinvitromodelofintermittenthypoxiainducedliverinjury
AT huangyaping expressionprofilingandfunctionalanalysisofcircularrnasinvitromodelofintermittenthypoxiainducedliverinjury
AT xuqiaozhen expressionprofilingandfunctionalanalysisofcircularrnasinvitromodelofintermittenthypoxiainducedliverinjury
AT chengongping expressionprofilingandfunctionalanalysisofcircularrnasinvitromodelofintermittenthypoxiainducedliverinjury
AT linqichang expressionprofilingandfunctionalanalysisofcircularrnasinvitromodelofintermittenthypoxiainducedliverinjury