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Micro RNA ‐661 modulates redox and metabolic homeostasis in colon cancer

2017; Elsevier BV; Volume: 11; Issue: 12 Linguagem: Inglês

10.1002/1878-0261.12142

1878-0261

Marta Gómez de Cedrón, Rebeca Acín‐Pérez, Ruth Sánchez‐Martínez, Susana Molina, Jesús Herránz, Jaime Feliú, Guillermo Reglero, José Antonio Enrı́quez, Ana Ramı́rez de Molina,

Cancer-related molecular mechanisms research

Cancer cell survival and metastasis are dependent on metabolic reprogramming that is capable of increasing resistance to oxidative and energetic stress. Targeting these two processes can be crucial for cancer progression. Herein, we describe the role of micro RNA ‐661 (miR661) as epigenetic regulator of colon cancer ( CC ) cell metabolism. MicroR661 induces a global increase in reactive oxygen species, specifically in mitochondrial superoxide anions, which appears to be mediated by decreased carbohydrate metabolism and pentose phosphate pathway, and by a higher dependency on mitochondrial respiration. MicroR661 overexpression in non‐metastatic human CC cells induces an epithelial‐to‐mesenchymal transition phenotype, and a reduced tolerance to metabolic stress. This seems to be a general effect of miR661 in CC , since metastatic CC cell metabolism is also compromised upon miR661 overexpression. We propose hexose‐6‐phosphate dehydrogenase and pyruvate kinase M2 as two key players related to the observed metabolic reprogramming. Finally, the clinical relevance of miR661 expression levels in stage‐ II and III CC patients is discussed. In conclusion, we propose miR661 as a potential modulator of redox and metabolic homeostasis in CC .