Purpose: In the early stage, bioinformatics analysis revealed that the expression of long-chain non-coding RNA LINC00963 in glioma tissues was remarkably increased, but its biological effects on glioma and the potential molecular mechanisms have not been reported. This study aimed to conduct a preliminary discussion on the impact of LINC00963 on glioma, so as to provide new ideas for the treatment of this cancer.
Methods: GEPIA database was consulted to determine the expression level of LINC00963 in gliomas. In addition, the interplay between LINC00963 expression and the prognosis of glioma patients was analyzed by Kaplan-Meier method. Effects of LINC00963 on the proliferation and migration of glioma cells were determined using Cell Counting Kit (CCK-8) and Transwell assay. The subcellular localization of LINC00963 was determined by nuclear separation experiments. At the same time, the regulation of LINC00963 on p21 expression was verified through qRT-PCR and Western blot experiments.
Results: By analyzing the GEPIA database, we found that LINC00963 was highly expressed in glioma tissues. Meanwhile, qRT-PCR results revealed that LINC00963 level in glioma tissues and cell lines was remarkably higher than that in the normal control group. Kaplan-Meier and log-rank test revealed that there was no statistically significant association between the expression level of LINC00963 and the prognosis of patients with glioma. In addition, in vitro cell assay results indicated that downregulation of LINC00963 markedly suppressed the proliferation and invasiveness of glioma cells. Finally, the related mechanism analysis revealed that LINC00963 may inhibit p21 expression through modulation of EZH2.
Conclusions: LINC00963 can inhibit p21 expression through EZH2 and thus enhance the proliferative and invasive capacities of glioma cells. Consequently, LINC00963 may be a potential therapeutic target for gliomas.
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Proc Natl Acad Sci U S A
January 2025
Department of Immunology and Regenerative Biology, Weizmann Institute of Science, Rehovot 7610001, Israel.
Malignant gliomas are heterogeneous tumors, mostly incurable, arising in the central nervous system (CNS) driven by genetic, epigenetic, and metabolic aberrations. Mutations in isocitrate dehydrogenase (IDH1/2) enzymes are predominantly found in low-grade gliomas and secondary high-grade gliomas, with IDH1 mutations being more prevalent. Mutant-IDH1/2 confers a gain-of-function activity that favors the conversion of a-ketoglutarate (α-KG) to the oncometabolite 2-hydroxyglutarate (2-HG), resulting in an aberrant hypermethylation phenotype.
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Department of Anesthesiology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, P.R. China.
The presence of specific genetic mutations in patients with glioblastoma multiforme (GBM) is associated with improved survival outcomes. Disruption of the DNA damage response (DDR) pathway in tumor cells enhances the effectiveness of radiotherapy drugs, while increased mutational burden following tumor cell damage also facilitates the efficacy of immunotherapy. The ATRX gene, located on chromosome X, plays a crucial role in DDR.
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January 2025
Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai 200040, China; National Center for Neurological Disorders, Shanghai 200040, China; Shanghai Key Laboratory of Brain Function and Restoration and Neural Regeneration, Shanghai 200040, China; Neurosurgical Institute of Fudan University, Shanghai 200040, China; Shanghai Clinical Medical Center of Neurosurgery, Shanghai 200040, China. Electronic address:
Glioblastoma (GBM) is a highly lethal malignant brain tumor with poor survival rates, and chemoresistance poses a significant challenge to the treatment of patients with GBM. Here, we show that transketolase (TKT), a metabolic enzyme in the pentose phosphate pathway (PPP), attenuates the chemotherapy sensitivity of glioma cells in a manner independent of catalytic activity. Mechanistically, chemotherapeutic drugs can facilitate the translocation of TKT protein from the cytosol into the nucleus, where TKT physically interacts with XRN2 to regulate the resolution and removal of R-loops.
View Article and Find Full Text PDFClin Neuropharmacol
January 2025
Department of Neurosurgery, Yubei District Hospital of TCM, Chongqing, China.
Objective: Gliomas are a general designation for neuroepithelial tumors derived from the glial cells of the central nervous system. According to the histopathological and immunohistochemical features, the World Health Organization classifies gliomas into four grades. Bevacizumab is a monoclonal antibody targeting vascular endothelial growth factor that has been approved for the treatment of glioblastoma multiforme (GBM) as a second-line therapy.
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January 2025
Department of Molecular Medicine and Pathology, School of Medical Sciences, Faculty of Medical and Health Sciences, University of Auckland, Auckland 1023, New Zealand.
The overall goal of this work was to assess the ability of Natural Killer cells to kill cultures of patient-derived glioblastoma cells. Herein we report impressive levels of NK-92 mediated killing of various patient-derived glioblastoma cultures observed at ET (effector: target) ratios of 5:1 and 1:1. This enabled direct comparison of the degree of glioblastoma cell loss across a broader range of glioblastoma cultures.
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