TY - JOUR
T1 - Proneural and mesenchymal glioma stem cells display major differences in splicing and lncRNA profiles
AU - Guardia, Gabriela D.A.
AU - Correa, Bruna R.
AU - Araujo, Patricia Rosa
AU - Qiao, Mei
AU - Burns, Suzanne
AU - Penalva, Luiz O.F.
AU - Galante, Pedro A.F.
N1 - Funding Information:
We thank all members of Galante laboratory for helpful discussions. Daniel T. Ohara for technical assistance and Dr. Ichiro Nakano for sharing GSC lines. This study was supported by a grant from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Brazil to PAFG and LOFP and by NIH 7R21CA175875-03. This study was partially supported by grants from Serrapilheira foundation and Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP; 2018/15579-8) to PAFG. GDAG and BRC were supported by fellowships from FAPESP (2017/19541-2) and (2013/25483-4 and 2013/07159-5), respectively. PRA was supported by CPRIT Training Grant - RP140105.
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41525-019-0108-5
DO - 10.1038/s41525-019-0108-5
M3 - Article
C2 - 31969990
AN - SCOPUS:85078035657
SN - 2056-7944
VL - 5
JO - npj Genomic Medicine
JF - npj Genomic Medicine
IS - 1
M1 - 2
ER -