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NPM1 as a potential therapeutic target for atypical teratoid/rhabdoid tumors

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dc.contributor.authorPhi, Ji Hoon-
dc.contributor.authorSun, Choong-Hyun-
dc.contributor.authorLee, Se-Hoon-
dc.contributor.authorLee, Seungmook-
dc.contributor.authorPark, Inho-
dc.contributor.authorChoi, Seung A-
dc.contributor.authorPark, Sung-Hye-
dc.contributor.authorLee, Ji Yeoun-
dc.contributor.authorWang, Kyu-Chang-
dc.contributor.authorKim, Seung-Ki-
dc.contributor.authorYun, Hongseok-
dc.contributor.authorPark, Chul-Kee-
dc.date.accessioned2019-11-07T00:06:02Z-
dc.date.available2019-11-07T09:08:14Z-
dc.date.issued2019-08-28-
dc.identifier.citationBMC Cancer, 19(1):848ko_KR
dc.identifier.issn1471-2407-
dc.identifier.urihttps://hdl.handle.net/10371/162626-
dc.description.abstractBackground
Atypical teratoid/rhabdoid tumors (AT/RTs) are highly malignant brain tumors with inactivation of the SMARCB1 gene, which play a critical role in genomic transcriptional control. In this study, we analyzed the genomic and transcriptomic profiles of human AT/RTs to discover new druggable targets.

Methods
Multiplanar sequencing analyses, including whole exome sequencing (WES), single nucleotide polymorphism (SNP) arrays, array comparative genomic hybridization (aCGH), and whole transcriptome sequencing (RNA-Seq), were performed on 4 AT/RT tissues. Validation of a druggable target was conducted using AT/RT cell lines.

Results
WES revealed that the AT/RT genome is extremely stable except for the inactivation of SMARCB1. However, we identified 897 significantly upregulated genes and 523 significantly downregulated genes identified using RNA-Seq, indicating that the transcriptional profiles of the AT/RT tissues changed substantially. Gene set enrichment assays revealed genes related to the canonical pathways of cancers, and nucleophosmin (NPM1) was the most significantly upregulated gene in the AT/RT samples. An NPM1 inhibitor (NSC348884) effectively suppressed the viability of 7 AT/RT cell lines. Network analyses showed that genes associated with NPM1 are mainly involved in cell cycle regulation. Upon treatment with an NPM1 inhibitor, cell cycle arrest at G1 phase was observed in AT/RT cells.

Conclusions
We propose that NPM1 is a novel therapeutic target for AT/RTs.
ko_KR
dc.description.sponsorshipThis research was supported by the Bio & Medical Technology Development Program (NRF-2018M3A9H3021707) and the Basic Science Research Program (NRF-2019R1A2C2005144) through the National Research Foundation of Korea (NRF) funded by the Ministry of Science & ICT of Republic of Korea and a grant from the Samsung SDS. The funders collaboratively provided grants to complete the sequencing, data analysis, in vitro experiments, and publication.ko_KR
dc.language.isoenko_KR
dc.publisherBioMed Centralko_KR
dc.subjectAtypical teratoid/rhabdoid tumorko_KR
dc.subjectNPM1ko_KR
dc.subjectNucleophosminko_KR
dc.titleNPM1 as a potential therapeutic target for atypical teratoid/rhabdoid tumorsko_KR
dc.typeArticleko_KR
dc.contributor.AlternativeAuthor피지훈-
dc.contributor.AlternativeAuthor선충현-
dc.contributor.AlternativeAuthor이세훈-
dc.contributor.AlternativeAuthor이승묵-
dc.contributor.AlternativeAuthor박인호-
dc.contributor.AlternativeAuthor이지연-
dc.contributor.AlternativeAuthor왕규창-
dc.contributor.AlternativeAuthor김승기-
dc.contributor.AlternativeAuthor윤홍석-
dc.contributor.AlternativeAuthor박철기-
dc.identifier.doi10.1186/s12885-019-6044-z-
dc.language.rfc3066en-
dc.rights.holderThe Author(s).-
dc.date.updated2019-09-01T03:54:18Z-
Appears in Collections:
College of Medicine/School of Medicine (의과대학/대학원)Pediatrics (소아과학전공)Journal Papers (저널논문_소아과학전공)
College of Medicine/School of Medicine (의과대학/대학원)Neurosurgery (신경외과학전공)Journal Papers (저널논문_신경외과학전공)
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