Glutaminase isoforms expression switches microRNA levels and oxidative status in glioblastoma cells
| العنوان: | Glutaminase isoforms expression switches microRNA levels and oxidative status in glioblastoma cells |
|---|---|
| المؤلفون: | Felipe C Souza, José A. Campos-Sandoval, Alison Colquhoun, Juan A. Segura, Clara Márquez-Torres, Juan de los Santos-Jiménez, Nieves Urbano-Polo, Carolina Lobo, María C. Gómez-García, Ana Peñalver, David Brøndegaard, Javier Márquez, José M. Matés, Janet Martín-Campos, Ralph J. DeBerardinis, Francisco J. Alonso, Mercedes Martín-Rufián, Carolina Cardona, Laura Castilla, Rui Curi, Tzuling Cheng |
| المساهمون: | [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, 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., This work was financially supported by Ministerio de Ciencia y Tecnología of Spain, RTI2018-096866-B-I00 (to JMM and JM) and Ministerio de Educación of Spain PHB2010-0014-PC (to JMM). RJD is supported by the Howard Hughes Medical Institute, the National Cancer Institute, the Cancer Prevention and Research Institute of Texas, and the Moody Foundation. Thanks are also due to CAPES/DGU 250/11, Brazil (to FCS, RC and AC). JDSJ is granted by FPU17/04084, Ministerio de Ciencia, Innovación y Universidades. |
| المصدر: | Journal of Biomedical Science Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP Journal of Biomedical Science, Vol 28, Iss 1, Pp 1-16 (2021) |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Anatomy::Cells::Cells, Cultured::Cell Line::Cell Line, Tumor [Medical Subject Headings], Enzimas, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Glutathione reductase, lcsh:Medicine, Antioxidantes, Isoenzimas, medicine.disease_cause, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Antioxidants [Medical Subject Headings], chemistry.chemical_compound, Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Biochemical Processes::Lipid Peroxidation [Medical Subject Headings], Pharmacology (medical), Phenomena and Processes::Metabolic Phenomena::Metabolism::Oxidative Stress [Medical Subject Headings], Diseases::Neoplasms::Neoplastic Processes [Medical Subject Headings], Cancer, MicroARNs, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Protein Isoforms [Medical Subject Headings], biology, microRNA, Glutaminase, Línea celular, Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Biochemical Processes::Protein Carbonylation [Medical Subject Headings], Estrés oxidativo, General Medicine, Diseases::Neoplasms [Medical Subject Headings], Glutathione, Neoplasias, Up-Regulation, Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Oxidoreductases::Oxidoreductases Acting on Sulfur Group Donors::Glutathione Reductase [Medical Subject Headings], Gene Expression Regulation, Neoplastic, Isoenzymes, Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Isoenzymes [Medical Subject Headings], Antioxidant enzymes, Glutatión, Lipid peroxidation, Down-Regulation, ENZIMAS OXIRREDUTORAS, Superoxide dismutase, Downregulation and upregulation, Cell Line, Tumor, Glutaminasa, medicine, Gene silencing, Humans, Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Growth Processes::Cell Proliferation [Medical Subject Headings], Molecular Biology, Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Biochemical Processes::Down-Regulation [Medical Subject Headings], Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Biochemical Processes::Up-Regulation [Medical Subject Headings], Research, lcsh:R, Diseases::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Germ Cell and Embryonal::Neuroectodermal Tumors::Neoplasms, Neuroepithelial::Glioma::Astrocytoma::Glioblastoma [Medical Subject Headings], Biochemistry (medical), Cell Biology, Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression Regulation::Gene Expression Regulation, Neoplastic [Medical Subject Headings], Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Antisense Elements (Genetics)::RNA, Antisense::MicroRNAs [Medical Subject Headings], MicroRNAs, Oxidative Stress, chemistry, biology.protein, Cancer research, Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Amidohydrolases::Glutaminase [Medical Subject Headings], Cell line, Glioblastoma, Oxidative stress, Peroxidación de lípido |
| الوصف: | 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. |
| وصف الملف: | application/pdf; image/x-ms-bmp; application/vnd.ms-excel; image/tiff |
| اللغة: | English |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::dfe3c3c8d1f05fa8484ca925451d826cTest https://hdl.handle.net/10668/17204Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....dfe3c3c8d1f05fa8484ca925451d826c |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |