Tomasetti Marco, Santarelli Lory, Neuzil Jiri, Dong Lanfeng
Polytechnic University of Marche, Ancona 60020, Italy.
Polytechnic University of Marche, Ancona 60020, Italy.
Mitochondrion. 2014 Nov;19 Pt A:29-38. doi: 10.1016/j.mito.2014.06.004. Epub 2014 Jun 21.
Mitochondria are critical regulators of cell metabolism; thus, mitochondrial dysfunction is associated with many metabolic disorders, including cancer. Altered metabolism is a common property of cancer cells that exhibit enhanced capacity to 'ferment' glucose to pyruvate and then lactate, even in the presence of sufficient oxygen to support mitochondrial metabolism. Recently, it was reported that microRNAs (miRNAs) regulate important signalling pathways in mitochondria and many of these miRNAs are deregulated in various cancers. Different regulatory mechanisms can control miRNA expression at the genetic or epigenetic level, thus affecting the biogenetic machinery via recruitment of specific transcription factors. Metabolic reprogramming that cancer cells undergo during tumorigenesis offers a wide range of potential targets to impair tumour progression. MiRNAs participate in controlling cancer cell metabolism by regulating the expression of genes whose protein products either directly regulate metabolic machinery or indirectly modulate the expression of metabolic enzymes, serving as master regulators. Thus, modulation of the level of miRNAs may provide a new approach for the treatment of neoplastic diseases.
线粒体是细胞代谢的关键调节因子；因此，线粒体功能障碍与包括癌症在内的许多代谢紊乱有关。代谢改变是癌细胞的一个共同特征，即使在有足够氧气支持线粒体代谢的情况下，癌细胞将葡萄糖“发酵”为丙酮酸然后再转化为乳酸的能力也会增强。最近有报道称，微小RNA（miRNA）可调节线粒体中的重要信号通路，并且许多此类miRNA在各种癌症中都存在失调。不同的调控机制可在基因或表观遗传水平上控制miRNA的表达，从而通过招募特定转录因子来影响生物发生机制。癌细胞在肿瘤发生过程中经历的代谢重编程提供了广泛的潜在靶点来损害肿瘤进展。miRNA通过调节其蛋白质产物直接调节代谢机制或间接调节代谢酶表达的基因的表达，作为主要调节因子参与控制癌细胞代谢。因此，调节miRNA的水平可能为肿瘤疾病的治疗提供一种新方法。
