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Impact of RNA binding proteins on abnormal regulation of splicing in glioblastoma

Grant number: 17/19541-2
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): May 01, 2018
Effective date (End): June 30, 2021
Field of knowledge:Biological Sciences - Genetics - Human and Medical Genetics
Principal researcher:Pedro Alexandre Favoretto Galante
Grantee:Gabriela Der Agopian Guardia
Home Institution: Hospital Sírio-Libanês. Sociedade Beneficente de Senhoras (SBSHSL). São Paulo , SP, Brazil


Glioblastoma multiforme (GBM) is the most common and aggressive tumor of the central nervous system. Since these tumors are highly invasive and refractory to conventional treatment, most patients diagnosed with GBM present an average survival of 14.6 months. Therefore, the development of more effective treatments against GBM is essential and it will bring benefit to a myriad of patients. The development of such treatments requires understanding all pathways that eventually contribute to tumor growth and therapy resistance. Splicing alterations affect all phenotypes associated with tumor development, including proliferation, apoptosis, cell adhesion, migration, invasion and immune system evasion. In this context, splicing factors have been initially investigated as potential therapeutic targets. The identification of such targets in GBM requires an investigation of the molecular mechanisms responsible for the abnormal regulation of splicing in this tumor type. This project aims to investigate splicing changes in GBM that may contribute to its greater aggressiveness in comparison to low-grade gliomas, also evaluating expression changes in splicing regulators. We intend to relate the splicing changes to the aberrant expression of splicing regulators, map oncogenic activation pathways affected by splicing regulation and identify isoforms that may potentially be used as therapeutic markers or targets. Furthermore, the prevalence and survival of patients with gliomas are associated with gender differences. However, the molecular mechanisms underlying these differences have not yet been elucidated from a genomic perspective. Thus, we will investigate how sexual dimorphism contributes to gliomas aggressiveness and whether splicing changes are an important component in this context.

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Scientific publications (5)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
FRAU, CARLA; JAMARD, CATHERINE; DELPOUVE, GASPARD; GUARDIA, GABRIELA D. A.; MACHON, CHRISTELLE; PILATI, CAMILLA; LE NEVE, CLEMENTINE; LAURENT-PUIG, PIERRE; GUITTON, JEROME; GALANTE, PEDRO A. F.; et al. Deciphering the Role of Intestinal Crypt Cell Populations in Resistance to Chemotherapy. Cancer Research, v. 81, n. 10, p. 2730-2744, . (17/19541-2)
KOSTI, ADAM; DE ARAUJO, PATRICIA ROSA; LI, WEI-QING; GUARDIA, GABRIELA D. A.; CHIOU, JENNIFER; YI, CAIHONG; RAY, DEBASHISH; MELISO, FABIANA; LI, YI-MING; DELAMBRE, TALIA; et al. The RNA-binding protein SERBP1 functions as a novel oncogenic factor in glioblastoma by bridging cancer metabolism and epigenetic regulation. Genome Biology, v. 21, n. 1, . (17/19541-2)
VELASCO, MITZLI X.; KOSTI, ADAM; GUARDIA, GABRIELA D. A.; SANTOS, MARCIA C.; TEGGE, ALLISON; QIAO, MEI; CORREA, BRUNA R. S.; HERNANDEZ, GRECO; KOKOVAY, ERZSEBET; GALANTE, PEDRO A. F.; et al. Antagonism between the RNA-binding protein Musashi1 and miR-137 and its potential impact on neurogenesis and glioblastoma development. RNA, v. 25, n. 7, p. 768-782, . (13/07159-5, 17/19541-2, 13/25483-4)
BARONI, MIRELLA; GUARDIA, GABRIELA D. A.; LEI, XIUFEN; KOSTI, ADAM; QIAO, MEI; LANDRY, TESHA; MAU, KARL; GALANTE, PEDRO A. F.; PENALVA, LUIZ O. F.. The RNA-Binding Protein Musashi1 Regulates a Network of Cell Cycle Genes in Group 4 Medulloblastoma. CELLS, v. 11, n. 1, . (17/19541-2, 18/15579-8)
GUARDIA, GABRIELA D. A.; CORREA, BRUNA R.; ARAUJO, PATRICIA ROSA; QIAO, MEI; BURNS, SUZANNE; PENALVA, LUIZ O. F.; GALANTE, PEDRO A. F.. Proneural and mesenchymal glioma stem cells display major differences in splicing and lncRNA profiles. NPJ GENOMIC MEDICINE, v. 5, n. 1, . (18/15579-8, 13/07159-5, 17/19541-2, 13/25483-4)

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