Background: Glutaminase isoenzymes GLS and GLS2 play apparently opposing roles in cancer: GLS acts as an oncoprotein, while GLS2 (GAB isoform) has context specific tumour suppressive activity. Some microRNAs (miRNAs) have been implicated in progression of tumours, including gliomas. The aim was to investigate the effect of GLS and GAB expression on both miRNAs and oxidative status in glioblastoma cells.
Methods: Microarray profiling of miRNA was performed in GLS-silenced LN229 and GAB-transfected T98G human glioblastoma cells and their wild-type counterparts. Results were validated by real-time quantitative RT-PCR. Oxidative status and antioxidant enzymes were determined by spectrophotometric or fluorescence assays in GLS-silenced LN229 and T98G, and GAB-transfected LN229 and T98G.
Results: MiRNA-146a-5p, miRNA-140-3p, miRNA-21-5p, miRNA-1260a, and miRNA-92a-3p were downregulated, and miRNA-1246 was upregulated when GLS was knocked down. MiRNA-140-3p, miRNA-1246, miRNA-1260a, miRNA-21-5p, and miRNA-146a-5p were upregulated when GAB was overexpressed. Oxidative status (lipid peroxidation, protein carbonylation, total antioxidant capacity, and glutathione levels), as well as antioxidant enzymes (catalase, superoxide dismutase, and glutathione reductase) of silenced GLS glioblastoma cells and overexpressed GAB glioblastoma cells significantly changed versus their respective control glioblastoma cells. MiRNA-1246, miRNA-1260a, miRNA-146a-5p, and miRNA-21-5p have been characterized as strong biomarkers of glioblastoma proliferation linked to both GLS silencing and GAB overexpression. Total glutathione is a reliable biomarker of glioblastoma oxidative status steadily associated to both GLS silencing and GAB overexpression.
Conclusions: Glutaminase isoenzymes are related to the expression of some miRNAs and may contribute to either tumour progression or suppression through certain miRNA-mediated pathways, proving to be a key tool to switch cancer proliferation and redox status leading to a less malignant phenotype. Accordingly, GLS and GAB expression are especially involved in glutathione-dependent antioxidant defence.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7897386 | PMC |
| http://dx.doi.org/10.1186/s12929-021-00712-y | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Basic Science and Pathogenesis.
Alzheimers Dement
December 2024
McGill University, Montreal, QC, Canada.
Background: Activation of the mTOR pathway is pivotal for microglia to induce and sustain neuroprotective functions (Ulland et al., 2017; Wang et al., 2022).
View Article and Find Full Text PDFBasic Science and Pathogenesis.
Alzheimers Dement
December 2024
Department of Neurosurgery, Maxine Dunitz Neurosurgical Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Background: Alzheimer's disease (AD) is the foremost cause of global dementia, also characterized by retinal changes involving Aβ, hyperphosphorylated-tau (p-tau), neuronal degeneration, and tissue atrophy. Mitochondrial-driven reactive oxygen species (ROS) production, linked to synaptic dysfunction, is common to various neurodegenerative conditions, including AD. Despite synaptic dysfunction being an early predictor of cognitive decline in AD, its occurrence in the AD retina is unexplored.
View Article and Find Full Text PDFBasic Science and Pathogenesis.
Alzheimers Dement
December 2024
Nova Southeastern University, Fort Lauderdale, FL, USA.
Background: Cerebral amyloid angiopathy (CAA), characterized by the accumulation of amyloid protein in the cerebral vasculature, is highly prevalent in Alzheimer's disease (AD) patients and, on its own, increases the risk of hemorrhagic stroke, cognitive impairment, and dementia. Currently, there are no effective ways to treat or prevent CAA. Ketogenic diet (KD), characterized by high-fat, low-carbohydrate, and moderate amounts of protein consumption, has gained considerable attention in recent years for its potential therapeutic use in patients with neurodegenerative diseases, including Alzheimer's disease.
View Article and Find Full Text PDFClinical Manifestations.
Alzheimers Dement
December 2024
Michigan Alzheimer's Disease Research Center, Ann Arbor, MI, USA.
Background: Sleep apnea, a common sleep disorder, has been associated with various health conditions, including arthritis. This study investigates the relationship between sleep apnea and arthritis, examining how demographic and clinical characteristics impact this association. There are several interrelations between sleep apnea and arthritis, one of which may be attributed to systemic inflammation and oxidative stress pathways commonly activated in both conditions.
View Article and Find Full Text PDFApigenin as an emerging hepatoprotective agent: current status and future perspectives.
Front Pharmacol
December 2024
School of Clinical Medical, Chengdu Medical College, Chengdu, China.
Apigenin (CHO, API) is a natural flavonoid widely found in vegetables, fruits, and plants such as celery, oranges, and chamomile. In recent years, API has attracted considerable attention as a dietary supplement due to its low toxicity, non-mutagenic properties and remarkable therapeutic efficacy in various diseases. In particular, evidence from a large number of preclinical studies suggests that API has promising effects in the prevention and treatment of a variety of liver diseases, including multifactorial liver injury, non-alcoholic fatty liver disease/non-alcoholic steatohepatitis, liver fibrosis and liver cancer.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!