Proneural and mesenchymal glioma stem cells display major differences in splicing and lncRNA profiles

Author(s)

Guardia, Gabriela D. A. ^[1] ; Correa, Bruna R. ^{[1, 2]} ; Araujo, Patricia Rosa ^[3] ; Qiao, Mei ^[3] ; Burns, Suzanne ^[3] ; Penalva, Luiz O. F. ^{[3, 4]} ; Galante, Pedro A. F. ^[1]

Affiliation

^[1] Hosp Sirio Libanes, Ctr Oncol Mol, BR-01309060 Sao Paulo, SP - Brazil

^[2] Barcelona Inst Sci & Technol, Ctr Genom Regulat CRG, Barcelona 08003, Catalonia - Spain

^[3] UT Hlth San Antonio, Childrens Canc Res Inst, San Antonio, TX 78229 - USA

^[4] UT Hlth San Antonio, Dept Cell Syst & Anat, San Antonio, TX 78229 - USA

• Document type: Journal article
• Source: NPJ GENOMIC MEDICINE; v. 5, n. 1 JAN 16 2020.
• Web of Science Citations: 0

Abstract

Therapy resistance and recurrence in high-grade gliomas are driven by their populations of glioma stem cells (GSCs). Thus, detailed molecular characterization of GSCs is needed to develop more effective therapies. We conducted a study to identify differences in the splicing profile and expression of long non-coding RNAs in proneural and mesenchymal GSC cell lines. Genes related to cell cycle, DNA repair, cilium assembly, and splicing showed the most differences between GSC subgroups. We also identified genes distinctly associated with survival among patients of mesenchymal or proneural subgroups. We determined that multiple long non-coding RNAs with increased expression in mesenchymal GSCs are associated with poor survival of glioblastoma patients. In summary, our study established critical differences between proneural and mesenchymal GSCs in splicing profiles and expression of long non-coding RNA. These splicing isoforms and lncRNA signatures may contribute to the uniqueness of GSC subgroups, thus contributing to cancer phenotypes and explaining differences in therapeutic responses. (AU)

• 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 Opportunities: Research Grants - Young Investigators Grants - Phase 2
• FAPESP's process: 13/07159-5 - RNA-binding proteins and post-transcriptional variations: influence on glioblastoma multiforme development
• Grantee: Bruna Renata Silva Corrêa
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 17/19541-2 - Impact of RNA binding proteins on abnormal regulation of splicing in glioblastoma
• Grantee: Gabriela Der Agopian Guardia
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 13/25483-4 - Identification and functional analysis of RNA binding proteins associated with the development of glioblastoma multiform
• Grantee: Bruna Renata Silva Corrêa
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate