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首页> 外文期刊>Journal of cellular physiology. >Function of DHX33 in promoting Warburg effect via regulation of glycolytic genes
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Function of DHX33 in promoting Warburg effect via regulation of glycolytic genes

机译:在促进Warburg效应通过DHX33的函数调节糖酵解的基因

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Cancer cells metabolize glucose through glycolysis to promote cell proliferation even with abundant oxygen. Multiple glycolysis genes are deregulated during cancer development. Despite intensive effort, the cause of their deregulation remains incompletely understood. Here in this study, we discovered that DHX33 plays a critical role in Warburg effect of cancer cells. DHX33 deficient cells have markedly reduced glycolysis activity. Through RNA-seq analysis, we found multiple critical genes involved in Warburg effect were downregulated after DHX33 deficiency. These genes include lactate dehydrogenase A (LDHA), pyruvate dehydrogenase ki-nase 1 (PDK1), pyruvate kinase muscle isoform 2 (PKM2), enolase 1 (ENO1), ENO2, hexokinase 1/2, among others. With LDHA, PDK1, and PKM2 as examples, we further revealed that DHX33 altered the epigenetic marks around the promoter of glycolytic genes. This is through DHX33 in complex with Gadd45a-a growth arrest and DNA damage protein. DHX33 is required for the loading of Gadd45a and DNA dioxygenase Tet1 at the promoter sites, which resulted in active DNA demethylation and enhanced histone H4 acetylation. We conclude that DHX33 changes local epigenetic marks in favor of the transcription of glycolysis genes to promote cancer cell proliferation. Our study highlights the significance of RNA helicase DHX33 in Warburg effect and cancer therapeutics.
机译:肿瘤细胞通过糖酵解代谢葡萄糖促进细胞增殖甚至与丰富氧气。在癌症的发展。努力,放松管制的原因依然存在不完全理解。发现DHX33起着至关重要的作用华宝癌细胞的效果。细胞有明显降低糖酵解的活动。通过RNA-seq分析,我们发现多个Warburg效应的关键基因表达下调后DHX33缺乏症。包括乳酸脱氢酶(LDHA),丙酮酸脱氢酶ki-nase 1(基因),丙酮酸激酶己糖激酶1/2,等等。PKM2为例,我们进一步发现DHX33改变周围的表观遗传标记糖酵解基因的启动子。在复杂DHX33 Gadd45a-a逮捕和增长DNA损伤蛋白质。加载Gadd45a和DNA加双氧酶Tet1启动子站点,导致积极的DNA脱甲基作用和增强的组蛋白H4乙酰化作用。表观遗传标记的转录糖酵解促进癌细胞的基因扩散。意义的RNA解旋酶DHX33华宝和癌症治疗效果。

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