MiR-200c-based metabolic modulation in glioblastoma cells as a strategy to overcome tumor chemoresistance

• Tipo: Artigo em Revista Científica Internacional
• Data: 2021

Autores

Cardoso, AM (Autor) Outra; Morais, CM (Autor) Outra; Sousa, M (Autor) Outra; Rebelo, O (Autor) Outra; Tao, H (Autor) Outra; Barbosa, M (Autor) Outra; de Lima, MCP (Autor) Outra; Jurado, AS (Autor) Outra

Revista

Título: Human Molecular Genetics

Vol. 30

Páginas: 2315-2331

ISSN: 0964-6906

Editora: Oxford University Press

Indexação

ISI Web of Knowledge - 1 Citação

Scopus - 1 Citação

Outras Informações

ID Authenticus: P-00V-TGJ

DOI: 10.1093/hmg/ddab193

Abstract (EN): 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 months, 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. [GRAPHICS] .

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 17