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Integrated profiling identifies NCOA3 as a prognostic factor in patients with glioma
Qian Luo1, Jiaying Yang1, Hailin Yin1
1Key Laboratory of Pathobiology, Department of Biomedical Science, College of Basic Medical Sciences, Ministry of Education, Jilin University, Changchun, 130021, China.
Abstract:
Nuclear receptor coactivator 3 (NCOA3) is associated with various cancers, but its function and mechanism in glioblastoma multiforme (GBM) are still unclear. Bioinformatics analysis, in vitro cell experiments (NCOA3 silencing (si-NCOA3) or NCOA3 small-molecule inhibitor SI-2), in vivo animal models, and metabolic level detection were used to elucidate the activity of NCOA3 in GBM. The data revealed that GBM tissues had NCOA3 overexpression, which was linked with poor prognosis. It regulates pathways related to glycolysis, the cell cycle, and immunosuppression. Functionally, si-NCOA3/SI-2 suppressed GBM cell proliferation and migration. In vivo, sh-NCOA3/SI-2 demonstrated anti-glioma effects. Metabolically, treatment with si-NCOA3/SI-2 reduced glucose uptake, pyruvate and lactate production, ATP levels, and glycolysis-related enzyme expression in GBM cells. Combination therapy with SI-2 and TMZ enhanced GBM cell sensitivity to TMZ. Single-cell RNA sequencing revealed high NCOA3 expression in glioma stem cells (GSCs). si-NCOA3 inhibited GSCs proliferation and self-renewal while reducing the expression of Nestin and SOX2. NCOA3 is an oncogene in GBM. In mechanism, NCOA3 promotes GBM progression by enhancing the Warburg effect. In addition, NCOA3 is also highly expressed in GSCs and significantly promotes their proliferation and self-renewal ability. NCOA3 may represent a promising therapeutic target for GBM.
Insights
Nuclear receptor coactivator 3 (NCOA3) drives glioblastoma multiforme (GBM) progression by boosting the Warburg effect and supporting glioma stem cells. Inhibiting NCOA3 shows therapeutic promise for GBM treatment.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Nuclear receptor coactivator 3 (NCOA3) is implicated in various cancers, but its specific role in glioblastoma multiforme (GBM) remains largely undefined.
- Understanding NCOA3's function is crucial for developing novel therapeutic strategies against GBM.
Purpose of the Study:
- To investigate the role and mechanism of NCOA3 in glioblastoma multiforme (GBM) progression.
- To evaluate NCOA3 as a potential therapeutic target for GBM.
Main Methods:
- Bioinformatics analysis, in vitro cell experiments (NCOA3 silencing/inhibition), in vivo animal models, and metabolic assays were employed.
- Single-cell RNA sequencing was utilized to assess NCOA3 expression in glioma stem cells (GSCs).
Main Results:
- NCOA3 was found to be overexpressed in GBM tissues, correlating with poor prognosis.
- NCOA3 inhibition suppressed GBM cell proliferation, migration, and enhanced sensitivity to temozolomide (TMZ).
- NCOA3 promotes GBM via the Warburg effect and supports GSC proliferation and self-renewal.
Conclusions:
- NCOA3 acts as an oncogene in GBM, promoting tumor progression by enhancing glycolysis (Warburg effect) and supporting GSCs.
- Targeting NCOA3 presents a promising therapeutic avenue for glioblastoma multiforme treatment.
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