MicroRNA regulation of cancer metabolism: role in tumour suppression

• Mitochondria are vital organelles essential for generation of cellular energy, provision of building intermediates for a variety of biosynthetic pathways as well as initiation of the intrinsic apoptotic pathway.
• MicroRNAs, small non-coding RNAs became a focus of researchers due to their involvement in the regulation of a plethora of processes and pathways in the context of both normal and pathological cellular physiology.
• In this review we discuss the role of microRNA in the regulation of the mitochondrial function in cancer, affecting both cancer and the adjacent stromal cells as well as the interaction between cancer cells and cells of the tumour stroma.
• We propose that microRNAs are a novel, attractive target for cancer therapy.

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.