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Deciphering the molecular mechanism of the THBS1 gene in the TNF signaling axis in glioma stem cells.
- Source :
-
Cellular signalling [Cell Signal] 2023 Jun; Vol. 106, pp. 110656. Date of Electronic Publication: 2023 Mar 17. - Publication Year :
- 2023
-
Abstract
- Glioma stem cells (GSCs) are thought to be responsible for the initiation and progression of glioblastoma (GBM). GBM presents highly invasive growth with a very high recurrence rate, so it has become a clinical problem to be solved urgently. RNAseq demonstrates that thrombospondin 1 (THBS1) acts not only in the angiogenic core of glioma but also with a high degree of invasiveness and infiltration. Nevertheless, defects in the signaling pathway research lead to a poor prognosis in glioma patients. To investigate the relevant molecular mechanism and signal pathway of glioma stem cell behavior mediated by THBS1, U251 astroglioma cells and GSCs were taken as model cells for in vitro experiments. The biological effects of THBS1 on glioma proliferation, migration, and adhesion were evaluated using Cell Counting Kit-8(CCK8) assays, EdU incorporation assays, migration assays, Transwell assays, Western blotting, and RNAseq. We found that the knockout of the THBS1 gene by CRISPR/Cas9 promoted proliferation and migration in U251 cells and GSCs, as well as influencing cell cycle progression by regulating the TNF/MAPK/NF-κB and TGF-β/Smad signaling pathways. Moreover, U251 cells and GSCs showed different responses to THBS1 knockout, suggesting specific and potential targets for GSCs in signaling pathways mediated by THBS1.<br />Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest.<br /> (Copyright © 2023. Published by Elsevier Inc.)
- Subjects :
- Humans
Cell Line, Tumor
Cell Proliferation genetics
Gene Expression Regulation, Neoplastic
Neoplastic Stem Cells metabolism
NF-kappa B metabolism
Signal Transduction
Thrombospondin 1 metabolism
Brain Neoplasms genetics
Brain Neoplasms metabolism
Glioblastoma metabolism
Glioma genetics
Glioma metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1873-3913
- Volume :
- 106
- Database :
- MEDLINE
- Journal :
- Cellular signalling
- Publication Type :
- Academic Journal
- Accession number :
- 36935087
- Full Text :
- https://doi.org/10.1016/j.cellsig.2023.110656