Inhibition of SIRT7 overcomes sorafenib acquired resistance by suppressing ERK1/2 phosphorylation via the DDX3X-mediated NLRP3 inflammasome in hepatocellular carcinoma
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dc.contributor.author | Kim, Yuna | - |
dc.contributor.author | Jung, Kwan-Young | - |
dc.contributor.author | Kim, Yun Hak | - |
dc.contributor.author | Xu, Pan | - |
dc.contributor.author | Kang, Baeki E. | - |
dc.contributor.author | Jo, Yunju | - |
dc.contributor.author | Pandit, Navin | - |
dc.contributor.author | Kwon, Jeongho | - |
dc.contributor.author | Gariani, Karim | - |
dc.contributor.author | Gariani, Joanna | - |
dc.contributor.author | Lee, Junguee | - |
dc.contributor.author | Verbeek, Jef | - |
dc.contributor.author | Nam, Seungyoon | - |
dc.contributor.author | Bae, Sung-Jin | - |
dc.contributor.author | Ha, Ki-Tae | - |
dc.contributor.author | Yi, Hyon-Seung | - |
dc.contributor.author | Shong, Minho | - |
dc.contributor.author | Kim, Kyun-Hwan | - |
dc.contributor.author | Kim, Doyoun | - |
dc.contributor.author | Jung, Hee Jung | - |
dc.contributor.author | Lee, Chang-Woo | - |
dc.contributor.author | Kim, Kwang Rok | - |
dc.contributor.author | Schoonjans, Kristina | - |
dc.contributor.author | Auwerx, Johan | - |
dc.contributor.author | Ryu, Dongryeol | - |
dc.date.accessioned | 2024-06-09T12:00:25Z | - |
dc.date.available | 2024-06-09T12:00:25Z | - |
dc.date.issued | 2024-03 | - |
dc.identifier.issn | 1368-7646 | - |
dc.identifier.issn | 1532-2084 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/91482 | - |
dc.description.abstract | Aims: Sirtuin 7 (SIRT7) plays an important role in tumor development, and has been characterized as a potent regulator of cellular stress. However, the effect of SIRT7 on sorafenib acquired resistance remains unclear and a possible anti-tumor mechanism beyond this process in HCC has not been clarified. We examined the therapeutic potential of SIRT7 and determined whether it functions synergistically with sorafenib to overcome chemoresistance. Methods: Cancer Genome Atlas-liver HCC data and unbiased gene set enrichment analyses were used to identify SIRT7 as a potential effector molecule in sorafenib acquired resistance. Two types of SIRT7 chemical inhibitors were developed to evaluate its therapeutic properties when synergized with sorafenib. Mass spectrometry was performed to discover a direct target of SIRT7, DDX3X, and DDX3X deacetylation levels and protein stability were explored. Moreover, an in vivo xenograft model was used to confirm anti-tumor effect of SIRT7 and DDX3X chemical inhibitors combined with sorafenib. Results: SIRT7 inhibition mediated DDX3X depletion can re-sensitize acquired sorafenib resistance by disrupting NLRP3 inflammasome assembly, finally suppressing hyperactive ERK1/2 signaling in response to NLRP3 inflammasome-mediated IL-1β inhibition. Conclusions: SIRT7 is responsible for sorafenib acquired resistance, and its inhibition would be beneficial when combined with sorafenib by suppressing hyperactive pro-cell survival ERK1/2 signaling. © 2024 The Authors | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | CHURCHILL LIVINGSTONE | - |
dc.title | Inhibition of SIRT7 overcomes sorafenib acquired resistance by suppressing ERK1/2 phosphorylation via the DDX3X-mediated NLRP3 inflammasome in hepatocellular carcinoma | - |
dc.type | Article | - |
dc.identifier.wosid | 001175598900001 | - |
dc.identifier.doi | 10.1016/j.drup.2024.101054 | - |
dc.identifier.bibliographicCitation | Drug Resistance Updates, v.73 | - |
dc.description.isOpenAccess | N | - |
dc.identifier.scopusid | 2-s2.0-85183497560 | - |
dc.citation.title | Drug Resistance Updates | - |
dc.citation.volume | 73 | - |
dc.type.docType | Article | - |
dc.publisher.location | 스코트랜드 | - |
dc.subject.keywordAuthor | DDX3X | - |
dc.subject.keywordAuthor | ERK1/2 phosphorylation | - |
dc.subject.keywordAuthor | Hepatocellular carcinoma | - |
dc.subject.keywordAuthor | SIRT7 inhibitor | - |
dc.subject.keywordAuthor | Sorafenib resistance | - |
dc.subject.keywordPlus | SIRTUINS | - |
dc.subject.keywordPlus | STRESS | - |
dc.subject.keywordPlus | ACETYLATION | - |
dc.subject.keywordPlus | DISEASE | - |
dc.subject.keywordPlus | HEALTH | - |
dc.subject.keywordPlus | DAMAGE | - |
dc.subject.keywordPlus | PERK | - |
dc.subject.keywordPlus | DNA | - |
dc.relation.journalResearchArea | Pharmacology & Pharmacy | - |
dc.relation.journalWebOfScienceCategory | Pharmacology & Pharmacy | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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