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- Title
Expression profiling and functional analysis of circular RNAs in vitro model of intermittent hypoxia-induced liver injury.
- Authors
Li-Da Chen; Jie-Feng Huang; Xue-Jun Lin; Ya-Ping Huang; Qiao-Zhen Xu; Gong-Ping Chen; Qi-Chang Lin
- Abstract
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 IHinduced 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 BRL3A cells. 98 circRNAs were identified as being dysregulated in IH-treated BRL3A 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.
- Subjects
CIRCULAR RNA; LIVER injuries; FUNCTIONAL analysis; RNA analysis; SLEEP apnea syndromes
- Publication
Frontiers in Physiology, 2022, Vol 13, p1
- ISSN
1664-042X
- Publication type
Article
- DOI
10.3389/fphys.2022.972407