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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 Musashi1 Regulates a Network of Cell Cycle Genes in Group 4 Medulloblastoma

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Author(s):
Baroni, Mirella [1] ; Guardia, Gabriela D. A. [2] ; Lei, Xiufen [1] ; Kosti, Adam [1, 3] ; Qiao, Mei [1] ; Landry, Tesha [1] ; Mau, Karl [1] ; Galante, Pedro A. F. [2] ; Penalva, Luiz O. F. [1, 3]
Total Authors: 9
Affiliation:
[1] UT Hlth San Antonio, Childrens Canc Res Inst, San Antonio, TX 78229 - USA
[2] Hosp Siriolibanes, Ctr Oncol Mol, BR-01308060 Sao Paulo - Brazil
[3] UT Hlth San Antonio, Dept Cell Syst & Anat, San Antonio, TX 78229 - USA
Total Affiliations: 3
Document type: Journal article
Source: CELLS; v. 11, n. 1 JAN 2022.
Web of Science Citations: 0
Abstract

Medulloblastoma is the most common malignant brain tumor in children. Treatment with surgery, irradiation, and chemotherapy has improved survival in recent years, but patients are frequently left with devastating neurocognitive and other sequelae. Patients in molecular subgroups 3 and 4 still experience a high mortality rate. To identify new pathways contributing to medulloblastoma development and create new routes for therapy, we have been studying oncogenic RNA-binding proteins. We defined Musashi1 (Msi1) as one of the main drivers of medulloblastoma development. The high expression of Msi1 is prevalent in Group 4 and correlates with poor prognosis while its knockdown disrupted cancer-relevant phenotypes. Genomic analyses (RNA-seq and RIP-seq) indicated that cell cycle and division are the main biological categories regulated by Msi1 in Group 4 medulloblastoma. The most prominent Msi1 targets include CDK2, CDK6, CCND1, CDKN2A, and CCNA1. The inhibition of Msi1 with luteolin affected the growth of CHLA-01 and CHLA-01R Group 4 medulloblastoma cells and a synergistic effect was observed when luteolin and the mitosis inhibitor, vincristine, were combined. These findings indicate that a combined therapeutic strategy (Msi1 + cell cycle/division inhibitors) could work as an alternative to treat Group 4 medulloblastoma. (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
FAPESP's process: 18/15579-8 - Retroelements: a driving force generating genetic novelties in the human and mouse genome
Grantee:Pedro Alexandre Favoretto Galante
Support type: Research Grants - Young Investigators Grants - Phase 2