Functional Characterization of Circadian Nuclear Receptors REV-ERBα and REV-ERBβ in Human Osteosarcoma Cell Cultures
DC Field | Value | Language |
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dc.contributor.author | Cho, Hana | - |
dc.contributor.author | Yun, Ahee | - |
dc.contributor.author | Kim, Joohee | - |
dc.contributor.author | Park, Eunjeong | - |
dc.contributor.author | Jung, Jong-Wha | - |
dc.contributor.author | Chung, Sooyoung | - |
dc.contributor.author | Son, Gi Hoon | - |
dc.date.accessioned | 2024-02-13T03:00:13Z | - |
dc.date.available | 2024-02-13T03:00:13Z | - |
dc.date.issued | 2024-01 | - |
dc.identifier.issn | 1661-6596 | - |
dc.identifier.issn | 1422-0067 | - |
dc.identifier.uri | https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/65431 | - |
dc.description.abstract | REV-ERB alpha and its paralog, REV-ERB beta, 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-ERB alpha is more responsible for regulating the NF-kappa Beta signaling pathway, whereas a group of extracellular matrix components requires REV-ERB beta 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. | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | Multidisciplinary Digital Publishing Institute (MDPI) | - |
dc.title | Functional Characterization of Circadian Nuclear Receptors REV-ERBα and REV-ERBβ in Human Osteosarcoma Cell Cultures | - |
dc.type | Article | - |
dc.publisher.location | 스위스 | - |
dc.identifier.doi | 10.3390/ijms25020770 | - |
dc.identifier.scopusid | 2-s2.0-85183285783 | - |
dc.identifier.wosid | 001150883200001 | - |
dc.identifier.bibliographicCitation | International Journal of Molecular Sciences, v.25, no.2 | - |
dc.citation.title | International Journal of Molecular Sciences | - |
dc.citation.volume | 25 | - |
dc.citation.number | 2 | - |
dc.type.docType | Article | - |
dc.description.isOpenAccess | Y | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Biochemistry & Molecular Biology | - |
dc.relation.journalResearchArea | Chemistry | - |
dc.relation.journalWebOfScienceCategory | Biochemistry & Molecular Biology | - |
dc.relation.journalWebOfScienceCategory | Chemistry, Multidisciplinary | - |
dc.subject.keywordPlus | TRANSCRIPTION | - |
dc.subject.keywordPlus | METABOLISM | - |
dc.subject.keywordPlus | BEHAVIOR | - |
dc.subject.keywordPlus | RHYTHM | - |
dc.subject.keywordPlus | HEME | - |
dc.subject.keywordAuthor | circadian clock | - |
dc.subject.keywordAuthor | circadian rhythm | - |
dc.subject.keywordAuthor | REV-ERBs | - |
dc.subject.keywordAuthor | U2OS cell | - |
dc.subject.keywordAuthor | transcriptome | - |
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