改变的细胞代谢是由于生长因子过度刺激导致的快速增殖期间癌症的基本适应。我们回顾了涉及癌症代谢改变的不同途径,包括有氧糖酵解,戊糖磷酸途径,从头脂肪酸合成,丝氨酸和甘氨酸代谢.虽然癌蛋白,c-MYC,HIF1α和p53是这种代谢重编程的主要驱动因素,microRNAs(miR)的转录后调节在精细调节该代谢重编程基础的关键代谢酶的需求中也起着重要作用。我们还结合了有关miRNA的文献数据,这些miRNA可能调节癌症中负责代谢重编程的40种代谢酶,从计算预测中获得额外的miRs。我们的分析表明:(1)代谢酶经常受到多个miR的调节,(2)预测算法的置信度分数可能有助于缩小功能性miR-mRNA相互作用,这可能值得进一步的实验验证。通过结合已知和预测的致癌转录因子(TFs)(c-MYC,HIF1α和p53),甾醇调节元件结合蛋白1(SREBP1),40种代谢酶,我们已经建立了调控癌症代谢重编程的miR和致癌TFs的第一个参考图谱之一。组合网络显示糖酵解酶通过p53、c-MYC、HIF1α,而丝氨酸中的基因,甘氨酸和一种碳代谢通过c-MYC调节,以及其他无法通过调查单个miRs来观察的监管组织,TFs,和目标基因。
Altered cellular metabolism is a fundamental adaptation of cancer during rapid proliferation as a result of growth factor overstimulation. We review different pathways involving metabolic alterations in cancers including aerobic glycolysis, pentose phosphate pathway, de novo fatty acid synthesis, and serine and glycine metabolism. Although oncoproteins, c-MYC, HIF1α and p53 are the major drivers of this metabolic reprogramming, post-transcriptional regulation by microRNAs (miR) also plays an important role in finely adjusting the requirement of the key metabolic enzymes underlying this metabolic reprogramming. We also combine the literature data on the miRNAs that potentially regulate 40 metabolic enzymes responsible for metabolic reprogramming in cancers, with additional miRs from computational prediction. Our analyses show that: (1) a metabolic enzyme is frequently regulated by multiple miRs, (2) confidence scores from prediction algorithms might be useful to help narrow down functional miR-mRNA interaction, which might be worth further experimental validation. By combining known and predicted interactions of oncogenic transcription factors (TFs) (c-MYC, HIF1α and p53), sterol regulatory element binding protein 1 (SREBP1), 40 metabolic enzymes, and regulatory miRs we have established one of the first reference maps for miRs and oncogenic TFs that regulate metabolic reprogramming in cancers. The combined network shows that glycolytic enzymes are linked to miRs via p53, c-MYC, HIF1α, whereas the genes in serine, glycine and one carbon metabolism are regulated via the c-MYC, as well as other regulatory organization that cannot be observed by investigating individual miRs, TFs, and target genes.