Please use this identifier to cite or link to this item:
https://doi.org/10.1038/s41408-021-00421-7
DC Field | Value | |
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dc.title | Myeloma-specific superenhancers affect genes of biological and clinical relevance in myeloma | |
dc.contributor.author | Jia, Yunlu | |
dc.contributor.author | Zhou, Jianbiao | |
dc.contributor.author | Tan, Tze King | |
dc.contributor.author | Chung, Tae-Hoon | |
dc.contributor.author | Wong, Regina Wan Ju | |
dc.contributor.author | Chooi, Jing-Yuan | |
dc.contributor.author | Lim, Julia Sze Lynn | |
dc.contributor.author | Sanda, Takaomi | |
dc.contributor.author | Ooi, Melissa | |
dc.contributor.author | De Mel, Sanjay | |
dc.contributor.author | Soekojo, Cinnie | |
dc.contributor.author | Chen, Yongxia | |
dc.contributor.author | Zhang, Enfan | |
dc.contributor.author | Cai, Zhen | |
dc.contributor.author | Shen, Peng | |
dc.contributor.author | Ruan, Jian | |
dc.contributor.author | Chng, Wee-Joo | |
dc.date.accessioned | 2021-11-11T06:44:51Z | |
dc.date.available | 2021-11-11T06:44:51Z | |
dc.date.issued | 2021-02-12 | |
dc.identifier.citation | Jia, Yunlu, Zhou, Jianbiao, Tan, Tze King, Chung, Tae-Hoon, Wong, Regina Wan Ju, Chooi, Jing-Yuan, Lim, Julia Sze Lynn, Sanda, Takaomi, Ooi, Melissa, De Mel, Sanjay, Soekojo, Cinnie, Chen, Yongxia, Zhang, Enfan, Cai, Zhen, Shen, Peng, Ruan, Jian, Chng, Wee-Joo (2021-02-12). Myeloma-specific superenhancers affect genes of biological and clinical relevance in myeloma. BLOOD CANCER JOURNAL 11 (2). ScholarBank@NUS Repository. https://doi.org/10.1038/s41408-021-00421-7 | |
dc.identifier.issn | 20445385 | |
dc.identifier.uri | https://scholarbank.nus.edu.sg/handle/10635/205901 | |
dc.description.abstract | Multiple myeloma (MM) is an aggressive plasma cell neoplasm characterized by genomic heterogeneity. Superenhancers (SEs) are defined as large clusters of enhancers in close genomic proximity, which regulate genes for maintaining cellular identity and promote oncogenic transcription to which cancer cells highly addicted. Here, we analyzed cis-regulatory elements in MM samples with H3K27ac ChIP-seq, to identify novel SE-associated genes involved in the myeloma pathogenesis. SEs and their associated genes in cancerous tissue were compared with the control samples, and we found SE analysis alone uncovered cell-lineage-specific transcription factors and well-known oncogenes ST3GAL6 and ADM. Using a transcriptional CDK7 inhibitor, THZ1, coupled with H3K27ac ChlP-seq, we identified MAGI2 as a novel SE-associated gene of myeloma cells. Elevated MAGI2 was related to myelomagenesis with gradual increased expression from MGUS, SMM to newly diagnosed and relapsed MM. High prevalence of MAGI2 was also associated with poor survival of MM patients. Importantly, inhibition of the SE activity associated with MAGI2 decreased MAGI2 expression, inhibited cell growth and induced cell apoptosis. Mechanistically, we revealed that the oncogenic transcription factor, MAF, directly bound to the SE region and activated gene transcription. In summary, the discoveries of these acquired SEs-associated genes and the novel mechanism by which they are regulated provide new insights into MM biology and MAGI2-MAF-SE regulatory circuit offer potential novel targets for disease treatment. | |
dc.language.iso | en | |
dc.publisher | SPRINGER NATURE | |
dc.source | Elements | |
dc.subject | Science & Technology | |
dc.subject | Life Sciences & Biomedicine | |
dc.subject | Oncology | |
dc.subject | Hematology | |
dc.type | Article | |
dc.date.updated | 2021-11-10T03:53:56Z | |
dc.contributor.department | CANCER SCIENCE INSTITUTE OF SINGAPORE | |
dc.contributor.department | DEAN'S OFFICE (MEDICINE) | |
dc.contributor.department | MEDICINE | |
dc.description.doi | 10.1038/s41408-021-00421-7 | |
dc.description.sourcetitle | BLOOD CANCER JOURNAL | |
dc.description.volume | 11 | |
dc.description.issue | 2 | |
dc.published.state | Published | |
Appears in Collections: | Elements Staff Publications |
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Myeloma-specific superenhancers affect genes of biological and clinical relevance in myeloma.pdf | 4.07 MB | Adobe PDF | OPEN | Published | View/Download |
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