2026-07-22T05:26:14Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/182642024-11-28T14:42:57Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16927
Repisalud
author
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.
authoraffiliation
[de los Santos-Jiménez,J; Campos-Sandoval,JA; Márquez-Torres,C; Urbano-Polo,N; Brøndegaard,D; Martín-Rufián,M; Lobo,C; Peñalver,A; Gómez-García,MC; Martín-Campos,J; Cardona,C; Castilla;L; Segura,JA; Alonso,FJ; Márquez,J; Matés,JM] Departamento de Biología Molecular y Bioquímica and Instituto de Investigación de Biomedicina de Málaga (IBIMA), Universidad de Málaga, Málaga, Spain. [da Costa Souza,F; Colquhoun,A] Department of Cell and Developmental Biology, Biomedical Sciences Institute, University of São Paulo, São Paulo, Brazil. [Cheng,T] IDEAYA Biosciences, South San Francisco, CA, USA. [Curi,R] Interdisciplinary Post-Graduate Program in Health Sciences, Cruzeiro do Sul University, São Paulo, Brazil. [DeBerardinis,RJ] Children’s Medical Center Research Institute, University of Texas Southwestern Medical Center (UTSMC), Dallas, TX, USA. [DeBerardinis,RJ] Department of Pediatrics, UTSMC, TX, Dallas, USA. [DeBerardinis,RJ] McDermott Center for Human Growth and Development, UTSMC, Dallas, TX, USA.
2024-02-19T15:25:11Z
2024-02-19T15:25:11Z
2021-02-20
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
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.
eng
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
research article