{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T09:20:11Z","timestamp":1774084811514,"version":"3.50.1"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"23","license":[{"start":{"date-parts":[[2021,7,10]],"date-time":"2021-07-10T00:00:00Z","timestamp":1625875200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Portuguese national funds via FCT\u2014Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","award":["UIDB\/04539\/2020"],"award-info":[{"award-number":["UIDB\/04539\/2020"]}]},{"name":"COMPETE 2020\u2014Operational Programme for Competitiveness and Internationalisation","award":["POCI-01-0145-FEDER-016390"],"award-info":[{"award-number":["POCI-01-0145-FEDER-016390"]}]},{"name":"Centro 2020 Regional Operational Programme","award":["CENTRO-01-0145-FEDER-000008"],"award-info":[{"award-number":["CENTRO-01-0145-FEDER-000008"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,11,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Glioblastoma (GB) is the most aggressive and common form of primary brain tumor characterized by fast proliferation, high invasion and resistance to current standard treatment. The average survival rate post-diagnosis is 14.6\u00a0months, despite the aggressive standard post-surgery radiotherapy concomitant with chemotherapy with temozolomide (TMZ). Currently, efforts are being endowed to develop new and more efficient therapeutic approaches capable to overcome chemoresistance, inhibit tumor progression and improve overall patient survival rate. Abnormal microRNA (miRNA) expression has been correlated with chemoresistance, proliferation and resistance to apoptosis, which result from their master regulatory role of gene expression. Altered cell metabolism, favoring glycolysis, was identified as an emerging cancer hallmark and has been described in GB, thus offering a new target for innovative GB therapies. In this work, we hypothesized that a gene therapy-based strategy consisting of the overexpression of a miRNA downregulated in GB and predicted to target crucial metabolic enzymes might promote a shift of GB cell metabolism, decreasing the glycolytic dependence of tumor cells and contributing to their sensitization to chemotherapy with TMZ. The increase of miR-200c levels in DBTRG cells resulted in downregulation of messenger RNA of enzymes involved in bioenergetics pathways and impaired cell metabolism and mobility. In addition, miR-200c overexpression prior to DBTRG cell exposure to TMZ resulted in cell cycle arrest. Overall, our results show that miR-200c overexpression could offer a way to overcome chemoresistance developed by GB cells in response to current standard chemotherapy, providing an improvement to current GB standard treatment, with benefit for patient outcome.<\/jats:p>","DOI":"10.1093\/hmg\/ddab193","type":"journal-article","created":{"date-parts":[[2021,7,8]],"date-time":"2021-07-08T11:13:42Z","timestamp":1625742822000},"page":"2315-2331","source":"Crossref","is-referenced-by-count":6,"title":["MiR-200c-based metabolic modulation in glioblastoma cells as a strategy to overcome tumor chemoresistance"],"prefix":"10.1093","volume":"30","author":[{"given":"Ana M","family":"Cardoso","sequence":"first","affiliation":[{"name":"CNC\u2014Center for Neuroscience and Cell Biology, CIBB\u2014Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, IIIUC\u2014Institute for Interdisciplinary Research, Coimbra, Portugal"}]},{"given":"Catarina M","family":"Morais","sequence":"additional","affiliation":[{"name":"CNC\u2014Center for Neuroscience and Cell Biology, CIBB\u2014Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, IIIUC\u2014Institute for Interdisciplinary Research, Coimbra, Portugal"},{"name":"Department of Life Sciences, University of Coimbra, Cal\u00e7ada Martim de Freitas, Coimbra 3000-456, Portugal"}]},{"given":"Madalena","family":"Sousa","sequence":"additional","affiliation":[{"name":"CNC\u2014Center for Neuroscience and Cell Biology, CIBB\u2014Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, IIIUC\u2014Institute for Interdisciplinary Research, Coimbra, Portugal"},{"name":"Department of Life Sciences, University of Coimbra, Cal\u00e7ada Martim de Freitas, Coimbra 3000-456, Portugal"}]},{"given":"Olinda","family":"Rebelo","sequence":"additional","affiliation":[{"name":"Neuropathology Laboratory, Neurology Service, University Hospital of Coimbra, Coimbra 3004-561, Portugal"}]},{"given":"Herm\u00ednio","family":"T\u00e3o","sequence":"additional","affiliation":[{"name":"Neurosurgery Service, University Hospital of Coimbra, Coimbra 3004-561, Portugal"}]},{"given":"Marcos","family":"Barbosa","sequence":"additional","affiliation":[{"name":"Neurosurgery Service, University Hospital of Coimbra, Coimbra 3004-561, Portugal"},{"name":"Faculty of Medicine, University of Coimbra, Coimbra 3000-548, Portugal"}]},{"given":"Maria C","family":"Pedroso de Lima","sequence":"additional","affiliation":[{"name":"CNC\u2014Center for Neuroscience and Cell Biology, CIBB\u2014Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, IIIUC\u2014Institute for Interdisciplinary Research, Coimbra, Portugal"}]},{"given":"Am\u00e1lia S","family":"Jurado","sequence":"additional","affiliation":[{"name":"CNC\u2014Center for Neuroscience and Cell Biology, CIBB\u2014Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, IIIUC\u2014Institute for Interdisciplinary Research, Coimbra, Portugal"},{"name":"Department of Life Sciences, University of Coimbra, Cal\u00e7ada Martim de Freitas, Coimbra 3000-456, Portugal"}]}],"member":"286","published-online":{"date-parts":[[2021,7,10]]},"reference":[{"key":"2021111806112210000_ref1","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1007\/s00401-007-0243-4","article-title":"The 2007 WHO classification of tumours of the central nervous system","volume":"114","author":"Louis","year":"2007","journal-title":"Acta Neuropathol."},{"key":"2021111806112210000_ref2","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.pharmthera.2015.05.005","article-title":"Glioblastoma multiforme: pathogenesis and treatment","volume":"152","author":"Alifieris","year":"2015","journal-title":"Pharmacol. 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