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dc.contributor.author정수영*
dc.date.accessioned2024-05-20T16:31:22Z-
dc.date.available2024-05-20T16:31:22Z-
dc.date.issued2024*
dc.identifier.issn1661-6596*
dc.identifier.otherOAK-34829*
dc.identifier.urihttps://dspace.ewha.ac.kr/handle/2015.oak/268500-
dc.description.abstractREV-ERBα and its paralog, REV-ERBβ, encoded by NR1D1 and NR1D2 genes, are key nuclear receptors that link the circadian timing system and metabolic homeostasis. Since heme is an endogenous ligand, REV-ERBs have been considered key components of the circadian molecular clock and can be pharmacologically targeted to treat various circadian rhythm-related diseases, such as cardiometabolic, inflammatory, and neuropsychiatric diseases, as well as cancer. REV-ERBs are believed to be functionally redundant and compensatory, although they often affect the expression of gene subsets in an isoform-specific manner. Therefore, this study aimed to identify the redundant and distinct roles of each isoform in controlling its target genes by comparing the transcriptome profiles of a panel of mutant U2OS human osteosarcoma cells in which either NR1D1 or NR1D2 was ablated. Indeed, our transcriptomic analyses revealed that most REV-ERB-regulated genes are controlled by redundant or even additive actions. However, the RNA expression profiles of each single mutant cell line also provide strong evidence for isoform-dependent actions. For example, REV-ERBα is more responsible for regulating the NF-κΒ signaling pathway, whereas a group of extracellular matrix components requires REV-ERBβ to maintain their expression. We found that REV-ERBs have isoform-selective functions in the regulation of certain circadian output pathways despite their overlapping roles in the circadian molecular clock. Thus, the development of isoform-selective REV-ERB modulators can help treat metabolic disturbances and certain types of cancer. © 2024 by the authors.*
dc.languageEnglish*
dc.publisherMultidisciplinary Digital Publishing Institute (MDPI)*
dc.subjectcircadian clock*
dc.subjectcircadian rhythm*
dc.subjectREV-ERBs*
dc.subjecttranscriptome*
dc.subjectU2OS cell*
dc.titleFunctional Characterization of Circadian Nuclear Receptors REV-ERBα and REV-ERBβ in Human Osteosarcoma Cell Cultures*
dc.typeArticle*
dc.relation.issue2*
dc.relation.volume25*
dc.relation.indexSCIE*
dc.relation.indexSCOPUS*
dc.relation.journaltitleInternational Journal of Molecular Sciences*
dc.identifier.doi10.3390/ijms25020770*
dc.identifier.wosidWOS:001150883200001*
dc.identifier.scopusid2-s2.0-85183285783*
dc.author.googleCho*
dc.author.googleHana*
dc.author.googleYun*
dc.author.googleAhee*
dc.author.googleKim*
dc.author.googleJoohee*
dc.author.googlePark*
dc.author.googleEunjeong*
dc.author.googleJung*
dc.author.googleJong-Wha*
dc.author.googleChung*
dc.author.googleSooyoung*
dc.author.googleSon*
dc.author.googleGi Hoon*
dc.contributor.scopusid정수영(7404292716)*
dc.date.modifydate20240527165305*
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