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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

The RNA-binding protein SERBP1 functions as a novel oncogenic factor in glioblastoma by bridging cancer metabolism and epigenetic regulation

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Kosti, Adam [1, 2] ; de Araujo, Patricia Rosa [1, 2] ; Li, Wei-Qing [1, 3] ; Guardia, Gabriela D. A. [4] ; Chiou, Jennifer [5] ; Yi, Caihong [1] ; Ray, Debashish [6] ; Meliso, Fabiana [4] ; Li, Yi-Ming [3] ; Delambre, Talia [1] ; Qiao, Mei [1] ; Burns, Suzanne S. [1] ; Lorbeer, Franziska K. [1] ; Georgi, Fanny [1] ; Flosbach, Markus [1] ; Klinnert, Sarah [1] ; Jenseit, Anne [1] ; Lei, Xiufen [1] ; Sandoval, Carolina Romero [1] ; Ha, Kevin [6] ; Zheng, Hong [6] ; Pandey, Renu [1] ; Gruslova, Aleksandra [7] ; Gupta, Yogesh K. [1] ; Brenner, Andrew [8] ; Kokovay, Erzsebet [2] ; Hughes, Timothy R. [6, 9, 10] ; Morris, Quaid D. [6, 9, 11] ; Galante, Pedro A. F. [4] ; Tiziani, Stefano [5] ; Penalva, Luiz O. F. [1, 2]
Total Authors: 31
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[1] UT Hlth San Antonio, Childrens Canc Res Inst, San Antonio, TX 78229 - USA
[2] UT Hlth San Antonio, Dept Cell Syst & Anat, San Antonio, TX 78229 - USA
[3] Second Mil Med Univ, Shanghai Changzheng Hosp, Shanghai - Peoples R China
[4] Hosp Sirio Libanes, Ctr Oncol Mol, BR-01309060 Sao Paulo, SP - Brazil
[5] Univ Texas Austin, Dell Med Sch, Dell Pediat Res Inst, Dept Nutr Sci, Austin, TX 78712 - USA
[6] Univ Toronto, Donnelly Ctr, Toronto, ON M5S 3E1 - Canada
[7] UT Hlth San Antonio, Dept Med, San Antonio, TX 78229 - USA
[8] UT Hlth San Antonio, Mays Canc Ctr, San Antonio, TX 78229 - USA
[9] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8 - Canada
[10] MaRS Ctr, Tanadian Inst Adv Res, 661 Univ Ave, Suite 505, Toronto, ON M5G 1M1 - Canada
[11] Univ Toronto, Dept Comp Sci, Toronto, ON M5T 3A1 - Canada
Total Affiliations: 11
Document type: Journal article
Source: Genome Biology; v. 21, n. 1 AUG 6 2020.
Web of Science Citations: 1

BackgroundRNA-binding proteins (RBPs) function as master regulators of gene expression. Alterations in RBP expression and function are often observed in cancer and influence critical pathways implicated in tumor initiation and growth. Identification and characterization of oncogenic RBPs and their regulatory networks provide new opportunities for targeted therapy.ResultsWe identify the RNA-binding protein SERBP1 as a novel regulator of glioblastoma (GBM) development. High SERBP1 expression is prevalent in GBMs and correlates with poor patient survival and poor response to chemo- and radiotherapy. SERBP1 knockdown causes delay in tumor growth and impacts cancer-relevant phenotypes in GBM and glioma stem cell lines. RNAcompete identifies a GC-rich region as SERBP1-binding motif; subsequent genomic and functional analyses establish SERBP1 regulation role in metabolic routes preferentially used by cancer cells. An important consequence of these functions is SERBP1 impact on methionine production. SERBP1 knockdown decreases methionine levels causing a subsequent reduction in histone methylation as shown for H3K27me3 and upregulation of genes associated with neurogenesis, neuronal differentiation, and function. Further analysis demonstrates that several of these genes are downregulated in GBM, potentially through epigenetic silencing as indicated by the presence of H3K27me3 sites.ConclusionsSERBP1 is the first example of an RNA-binding protein functioning as a central regulator of cancer metabolism and indirect modulator of epigenetic regulation in GBM. By bridging these two processes, SERBP1 enhances glioma stem cell phenotypes and contributes to GBM poorly differentiated state. (AU)

FAPESP's process: 17/19541-2 - Impact of RNA binding proteins on abnormal regulation of splicing in glioblastoma
Grantee:Gabriela Der Agopian Guardia
Support type: Scholarships in Brazil - Post-Doctorate