RT Journal Article
T1 Glutaminase isoforms expression switches microRNA levels and oxidative status in glioblastoma cells
A1 de los Santos-Jiménez, Juan
A1 Campos-Sandoval, José A.
A1 Márquez-Torres, Clara
A1 Urbano-Polo, Nieves
A1 Brøndegaard, David
A1 Martín-Rufián, Mercedes
A1 Lobo, Carolina
A1 Peñalver, Ana
A1 Gómez-García, María C.
A1 Martín-Campos, Janet
A1 Cardona, Carolina
A1 Castilla, Laura
A1 da Costa Souza, Felipe
A1 Cheng, Tzuling
A1 Segura, Juan A.
A1 Alonso, Francisco J.
A1 Curi, Rui
A1 Colquhoun, Alison
A1 DeBerardinis, Ralph J.
A1 Márquez, Javier
A1 Matés, José M.
K1 Antioxidant enzymes
K1 Cancer
K1 Glioblastoma
K1 Glutaminase
K1 MicroRNA
K1 Oxidative stress
K1 Cell line
K1 Lipid peroxidation
K1 Glutathione
K1 Isoenzymes
K1 Antioxidantes
K1 Enzimas
K1 Neoplasias
K1 Glutaminasa
K1 MicroARNs
K1 Estrés oxidativo
K1 Línea celular
K1 Peroxidación de lípido
K1 Glutatión
K1 Isoenzimas
AB BackgroundGlutaminase 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.MethodsMicroarray 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.ResultsMiRNA-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.ConclusionsGlutaminase 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.
PB BioMed Central, Springer Nature
SN 1021-7770
YR 2021
FD 2021-02-20
LK http://hdl.handle.net/10668/4511
UL http://hdl.handle.net/10668/4511
LA en
NO de Los Santos-Jiménez J, Campos-Sandoval JA, Márquez-Torres C, Urbano-Polo N, Brøndegaard D, Martín-Rufián M, et al. Glutaminase isoforms expression switches microRNA levels and oxidative status in glioblastoma cells. J Biomed Sci. 2021 Feb 20;28(1):14
DS RISalud
RD Apr 14, 2025