Identification of novel functions of the ROCK2-specific inhibitor KD025 by bioinformatics analysis
DC Field | Value | Language |
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dc.contributor.author | Park J. | - |
dc.contributor.author | Chun K.-H. | - |
dc.date.available | 2020-04-06T07:38:18Z | - |
dc.date.created | 2020-04-02 | - |
dc.date.issued | 2020-05 | - |
dc.identifier.issn | 0378-1119 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/26424 | - |
dc.description.abstract | Rho-associated protein kinases (ROCKs) have various cellular functions, which include actin cytoskeleton remodeling and vesicular trafficking, and there are two major mammalian ROCK isotypes, namely, ROCK1 (ROKβ) and ROCK2 (ROKα). The ROCK2-specific inhibitor KD025 (SLx-2119) is currently undergoing phase II clinical trials, but its cellular functions have not been fully explored. In this study, we investigated the functions of KD025 at the genomics level by bioinformatics analysis using the GSE8686 microarray dataset from the NCBI GEO database, in three different primary human cell lines. An initial microarray analysis conducted by Boerma et al. focused on the effects of KD025 on cell adhesion and blood coagulation, but did not provide comprehensive information on the functions of KD025. Our analysis of differentially expressed genes (DEGs) showed ~70% coincidence with Boerma et al.’s findings, and newly identified that CCND1, CXCL2, NT5E, and SMOX were differentially expressed by KD025. However, due to low numbers of co-regulated DEGs, we were unable to extract the functions of KD025 with significance. To overcome this limitation, we used gene set enrichment analysis (GSEA) and the heatmap hierarchical clustering method. We confirmed KD025 regulated inflammation and adipogenesis pathways, as previously reported experimentally. In addition, we found KD025 has novel regulatory functions on various pathways, including oxidative phosphorylation, WNT signaling, angiogenesis, and KRAS signaling. Further studies are required to systematically characterize these newly identified functions of KD025. © 2020 Elsevier B.V. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | Elsevier B.V. | - |
dc.relation.isPartOf | Gene | - |
dc.title | Identification of novel functions of the ROCK2-specific inhibitor KD025 by bioinformatics analysis | - |
dc.type | Article | - |
dc.type.rims | ART | - |
dc.description.journalClass | 1 | - |
dc.identifier.wosid | 000523626800018 | - |
dc.identifier.doi | 10.1016/j.gene.2020.144474 | - |
dc.identifier.bibliographicCitation | Gene, v.737 | - |
dc.description.isOpenAccess | N | - |
dc.identifier.scopusid | 2-s2.0-85079835608 | - |
dc.citation.title | Gene | - |
dc.citation.volume | 737 | - |
dc.contributor.affiliatedAuthor | Park J. | - |
dc.contributor.affiliatedAuthor | Chun K.-H. | - |
dc.type.docType | Article | - |
dc.subject.keywordAuthor | Gene set enrichment analysis | - |
dc.subject.keywordAuthor | GSE8686 | - |
dc.subject.keywordAuthor | GSEA | - |
dc.subject.keywordAuthor | KD025 | - |
dc.subject.keywordAuthor | Microarray | - |
dc.subject.keywordAuthor | SLx-2119 | - |
dc.subject.keywordPlus | kd 025 | - |
dc.subject.keywordPlus | Rho kinase inhibitor | - |
dc.subject.keywordPlus | unclassified drug | - |
dc.subject.keywordPlus | adipogenesis | - |
dc.subject.keywordPlus | angiogenesis | - |
dc.subject.keywordPlus | Article | - |
dc.subject.keywordPlus | bioinformatics | - |
dc.subject.keywordPlus | blood clotting | - |
dc.subject.keywordPlus | CCND1 gene | - |
dc.subject.keywordPlus | cell adhesion | - |
dc.subject.keywordPlus | cluster analysis | - |
dc.subject.keywordPlus | controlled study | - |
dc.subject.keywordPlus | CXCL2 gene | - |
dc.subject.keywordPlus | DEG gene | - |
dc.subject.keywordPlus | gene expression | - |
dc.subject.keywordPlus | gene expression regulation | - |
dc.subject.keywordPlus | gene function | - |
dc.subject.keywordPlus | gene set enrichment analysis | - |
dc.subject.keywordPlus | genetic analysis | - |
dc.subject.keywordPlus | genetic database | - |
dc.subject.keywordPlus | genetic identification | - |
dc.subject.keywordPlus | genomics | - |
dc.subject.keywordPlus | heatmap hierarchical clustering method | - |
dc.subject.keywordPlus | human | - |
dc.subject.keywordPlus | human cell | - |
dc.subject.keywordPlus | inflammation | - |
dc.subject.keywordPlus | KRAS signaling | - |
dc.subject.keywordPlus | microarray analysis | - |
dc.subject.keywordPlus | NT5E gene | - |
dc.subject.keywordPlus | oxidative phosphorylation | - |
dc.subject.keywordPlus | priority journal | - |
dc.subject.keywordPlus | signal transduction | - |
dc.subject.keywordPlus | SMOX gene | - |
dc.subject.keywordPlus | Wnt signaling | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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