2026-07-22T05:26:11Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/182642024-11-28T14:42:57Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16927

00925njm 22002777a 4500 dc de los Santos-Jiménez, Juan author Campos-Sandoval, José A. author Márquez-Torres, Clara author Urbano-Polo, Nieves author Brøndegaard, David author Martín-Rufián, Mercedes author Lobo, Carolina author Peñalver, Ana author Gómez-García, María C. author Martín-Campos, Janet author Cardona, Carolina author Castilla, Laura author da Costa Souza, Felipe author Cheng, Tzuling author Segura, Juan A. author Alonso, Francisco J. author Curi, Rui author Colquhoun, Alison author DeBerardinis, Ralph J. author Márquez, Javier author Matés, José M. author 2021-02-20 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. 10.1186/s12929-021-00712-y 1423-0127 1021-7770 Journal of Biomedical Science http://hdl.handle.net/10668/4511 33610185 http://hdl.handle.net/20.500.12105/18264 Antioxidant enzymes Cancer Glioblastoma Glutaminase MicroRNA Oxidative stress Cell line Lipid peroxidation Glutathione Isoenzymes Antioxidantes Enzimas Neoplasias Glutaminasa MicroARNs Estrés oxidativo Línea celular Peroxidación de lípido Glutatión Isoenzimas Glutaminase isoforms expression switches microRNA levels and oxidative status in glioblastoma cells