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Conference Paper: A framework for identifying dysregulated chromatin regulators as master regulators in human cancer

TitleA framework for identifying dysregulated chromatin regulators as master regulators in human cancer
Authors
Issue Date2018
PublisherInsight Medical Publishing. The Journal's web site is located at http://www.acanceresearch.com/
Citation
International Conference on Immuno-Oncology and Cancer Science, Amsterdam, the Netherlands, 23- 24 July 2018. Proceedings in Archives in Cancer Research, 2018, v. 6 How to Cite?
AbstractChromatin regulators (CRs) are frequently dysregulated to reprogram the epigenetic landscape of the cancer genome. However, the underpinnings of the dysregulation of CRs and their downstream effectors remain to be elucidated. Here, we designed an integrated framework based on multi-omics data to identify candidate master regulator CRs affected by genomic alterations across eight cancer types in The Cancer Genome Atlas. Most of them showed consistent activated or repressed (i.e., oncogenic or tumor-suppressive) roles in cancer initiation and progression. In order to further explore the insight mechanism of the dysregulated CRs, we also developed an R package ModReg based on differential connectivity to recognize CRs as modulators of the transcription factors (TFs) involved in tumorigenesis. Our analysis revealed that the connectivity between TFs and their target genes tended to be disrupted in the patients who had a high expression of oncogenic CRs or low expression of tumor-suppressive CRs. As a proof-of-principle study, 14 (82.4%) of the top ranked 17 driver CRs in liver cancer were validated by literature mining or experiments including shRNA knockdown and dCas9 epigenetic editing. Moreover, we confirmed that chromatin regulator SIRT7 physically interacted with transcription factor NFE2L2, and positively modulated the transcriptional program of NFE2L2 by affecting ~64% of its targets.
DescriptionKeynote Forum [doi:10.21767/2254-6081-C2-007]
Persistent Identifierhttp://hdl.handle.net/10722/267834
ISSN

 

DC FieldValueLanguage
dc.contributor.authorZhang, J-
dc.date.accessioned2019-03-04T09:49:41Z-
dc.date.available2019-03-04T09:49:41Z-
dc.date.issued2018-
dc.identifier.citationInternational Conference on Immuno-Oncology and Cancer Science, Amsterdam, the Netherlands, 23- 24 July 2018. Proceedings in Archives in Cancer Research, 2018, v. 6-
dc.identifier.issn2254-6081-
dc.identifier.urihttp://hdl.handle.net/10722/267834-
dc.descriptionKeynote Forum [doi:10.21767/2254-6081-C2-007]-
dc.description.abstractChromatin regulators (CRs) are frequently dysregulated to reprogram the epigenetic landscape of the cancer genome. However, the underpinnings of the dysregulation of CRs and their downstream effectors remain to be elucidated. Here, we designed an integrated framework based on multi-omics data to identify candidate master regulator CRs affected by genomic alterations across eight cancer types in The Cancer Genome Atlas. Most of them showed consistent activated or repressed (i.e., oncogenic or tumor-suppressive) roles in cancer initiation and progression. In order to further explore the insight mechanism of the dysregulated CRs, we also developed an R package ModReg based on differential connectivity to recognize CRs as modulators of the transcription factors (TFs) involved in tumorigenesis. Our analysis revealed that the connectivity between TFs and their target genes tended to be disrupted in the patients who had a high expression of oncogenic CRs or low expression of tumor-suppressive CRs. As a proof-of-principle study, 14 (82.4%) of the top ranked 17 driver CRs in liver cancer were validated by literature mining or experiments including shRNA knockdown and dCas9 epigenetic editing. Moreover, we confirmed that chromatin regulator SIRT7 physically interacted with transcription factor NFE2L2, and positively modulated the transcriptional program of NFE2L2 by affecting ~64% of its targets.-
dc.languageeng-
dc.publisherInsight Medical Publishing. The Journal's web site is located at http://www.acanceresearch.com/-
dc.relation.ispartofArchives in Cancer Research-
dc.relation.ispartofInternational Conference on Immuno-Oncology and Cancer Science-
dc.titleA framework for identifying dysregulated chromatin regulators as master regulators in human cancer-
dc.typeConference_Paper-
dc.identifier.emailZhang, J: jzhang1@hku.hk-
dc.identifier.authorityZhang, J=rp01713-
dc.identifier.hkuros291166-
dc.identifier.volume6-
dc.publisher.placeUnited Kingdom-

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