RESUMO
Metabolic remodeling is a strategy for tumor survival under stress. However, the molecular mechanisms during the metabolic remodeling of colorectal cancer (CRC) remain unclear. Melanocyte proliferating gene 1 (MYG1) is a 3'-5' RNA exonuclease and plays a key role in mitochondrial functions. Here, we uncover that MYG1 expression is upregulated in CRC progression and highly expressed MYG1 promotes glycolysis and CRC progression independent of its exonuclease activity. Mechanistically, nuclear MYG1 recruits HSP90/GSK3ß complex to promote PKM2 phosphorylation, increasing its stability. PKM2 transcriptionally activates MYC and promotes MYC-medicated glycolysis. Conversely, c-Myc also transcriptionally upregulates MYG1, driving the progression of CRC. Meanwhile, mitochondrial MYG1 on the one hand inhibits oxidative phosphorylation (OXPHOS), and on the other hand blocks the release of Cyt c from mitochondria and inhibits cell apoptosis. Clinically, patients with KRAS mutation show high expression of MYG1, indicating a high level of glycolysis and a poor prognosis. Targeting MYG1 may disturb metabolic balance of CRC and serve as a potential target for the diagnosis and treatment of CRC.
Assuntos
Neoplasias Colorretais , Glicólise , Mitocôndrias , Fosforilação Oxidativa , Animais , Feminino , Humanos , Masculino , Camundongos , Apoptose/genética , Proteínas de Transporte/metabolismo , Proteínas de Transporte/genética , Linhagem Celular Tumoral , Núcleo Celular/metabolismo , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Regulação Neoplásica da Expressão Gênica , Glicogênio Sintase Quinase 3 beta/metabolismo , Glicogênio Sintase Quinase 3 beta/genética , Proteínas de Choque Térmico HSP90/metabolismo , Proteínas de Choque Térmico HSP90/genética , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Camundongos Nus , Mitocôndrias/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas de Ligação a Hormônio da Tireoide , Hormônios Tireóideos/metabolismo , Hormônios Tireóideos/genéticaRESUMO
The structures and physicochemical properties of ginkgo starches from seven cultivars were investigated and their relationships analyzed. The ginkgo starches had oval or irregular shapes, size distributions with a unimodal peak, and an A-type crystal pattern. The fine structures, crystalline structures, and physicochemical properties varied significantly among these ginkgo starches. Pearson correlation analysis and a PCA loading plot indicated that amylopectin A-chains and amylose had negative effects on the IR ratio, Imax, and D, while amylopectin B-chains had a clear positive effect on the relative crystallinity. Furthermore, the amylopectin short B1-chains and long B-chains contributed amorphous and single-helix structures, respectively. The thermal properties of the ginkgo starches were mainly influenced by the amylopectin B-chains and Imax, while the pasting properties were mainly influenced by amylopectin B-chains and helical structures. These results indicated that the starch fine structures and crystalline structures had significant effects on the physicochemical properties.