Non-coding RNAs, metabolic stress and adaptive mechanisms in cancer
Non-coding RNAs, metabolic stress and adaptive mechanisms in cancer
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非编码RNA、癌症中的代谢应激和适应机制
DOI：
10.1016/j.canlet.2020.06.024
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发表时间：
2020
期刊：
影响因子：
9.7
通讯作者：
Thorne Rick F.
中科院分区：
文献类型：
--
作者：
Liu Xiaoying;Feng Shanshan;Zhang Xu Dong;Li Jinming;Zhang Kaiguang;Wu Mian;Thorne Rick F.
癌症中的代谢重编程描述了有助于肿瘤发生的代谢的多方面变化。代谢表型的主要决定因素是与致癌激活相关的信号通路的变化以及来自肿瘤微环境的信号。在这种情况下，耗尽的氧气和营养水平会引发新陈代谢压力，需要癌细胞参与适应机制。非编码RNA(NcRNAs)作为代谢途径中的调节元件，其在癌症中广泛存在的失调导致代谢表型的改变。事实上，ncRNAs是许多重要的代谢重编程效应因子的调节帮凶，包括由代谢应激激活的c-myc和HIF。通过举例说明了在DNA-RNA-蛋白质生命周期中影响这些效应器的ncRNAs机制的范围，以及ncRNAs在对葡萄糖、谷氨酰胺和脂肪剥夺的适应性反应中的机制作用。我们还讨论了ncRNAs对代谢酶的兼性激活，这一现象可能反映了广泛但目前看不见的代谢调节水平。最后，讨论了与ncRNA发现相关的翻译挑战，强调了知识中的差距以及理解ncRNA调控机制的分子基础的重要性。
Metabolic reprogramming in cancer describes the multifaceted alterations in metabolism that contribute to tumorigenesis. Major determinants of metabolic phenotypes are the changes in signalling pathways associated with oncogenic activation together with cues from the tumor microenvironment. Therein, depleted oxygen and nutrient levels elicit metabolic stress, requiring cancer cells to engage adaptive mechanisms. Non-coding RNAs (ncRNAs) act as regulatory elements within metabolic pathways and their widespread dysregulation in cancer contributes to altered metabolic phenotypes. Indeed, ncRNAs are the regulatory accomplices of many prominent effectors of metabolic reprogramming including c-MYC and HIFs that are activated by metabolic stress. By example, this review illustrates the range of ncRNAs mechanisms impacting these effectors throughout their DNA-RNA-protein lifecycle along with presenting the mechanistic roles of ncRNAs in adaptive responses to glucose, glutamine and lipid deprivation. We also discuss the facultative activation of metabolic enzymes by ncRNAs, a phenomenon which may reflect a broad but currently invisible level of metabolic regulation. Finally, the translational challenges associated with ncRNA discoveries are discussed, emphasizing the gaps in knowledge together with importance of understanding the molecular basis of ncRNA regulatory mechanisms.