Microtargeting cancer metabolism: opening new therapeutic windows based on lipid metabolism

Metabolic reprogramming has emerged as a hallmark of cancer. MicroRNAs are noncoding RNAs that posttranscriptionally repress the expression of target mRNAs implicated in multiple physiological processes, including apoptosis, differentiation, and cancer. MicroRNAs can affect entire biological pathways, making them good candidates for therapeutic intervention compared with classical single target approaches. Moreover, microRNAs may become more relevant in the fine-tuning adaptation to stress situations, such as oncogenic events, hypoxia, nutrient deprivation, and oxidative stress. Furthermore, artificial microRNAs can be designed to modulate the expression of multiple targets of a specific pathway. In this review, we describe the metabolic reprogramming associated to cancer, with a special interest in the altered lipid metabolism. Next, we describe specific features of microRNAs that make them relevant to target cancer cell metabolism. Finally, in an attempt to open new therapeutic windows, we emphasize two exciting scenarios for microRNA-mediated intervention that need to be further explored: 1) the cooperation between FA biosynthesis (lipogenesis) and FA oxidation as complementary partners for the survival of cancer cells; and 2) the regulation of the intracellular lipid content modulating both lipid storage into lipid droplets, and lipid mobilization through lipolysis and/or lipophagy.