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

Abstract

and fl exibility to adapt to the microenvironment (oxygen, pH, and nutrient availability) ( 2-4 ).MicroRNAs are small single-stranded noncoding RNAs (19-25 nucleotides) that posttranscriptionally repress the expression of mRNAs implicated in nearly all cellular processes, such as cell cycle, apoptosis, autophagy, stemness, differentiation, angiogenesis, infl ammation, drug resistance, stress response, transformation, and migration. MicroRNAs are frequently deregulated in cancer and so they are important biomarkers for diagnosis and prognosis of the cellular outcome ( 5,6 ) Importantly, individual microRNAs, combinations of microRNAs, or even artifi cial microRNAs can specifi cally be designed to affect entire biological pathways ( 7,8 ), and this makes them good candidates for therapeutic intervention compared with classical single target approaches.In this review, we briefl y describe the altered cancer cell metabolism, and then we discuss the use of microRNAs as modulators of specifi c metabolic pathways in cancer (summarized in Fig. 1 ). We note the promising potentiallity of microRNAs for therapeutic intervention toward the altered lipid metabolism in cancer (summarized in Fig. 2 ). 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 (FAO) as a survival mechanism in cancer; and 2 ) the regulation of the intracellular lipid content in the Abstract 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 fi ne-tuning adaptation to stress situations, such as oncogenic events, hypoxia, nutrient deprivation, and oxidative stress. Furthermore, artifi cial microRNAs can be designed to modulate the expression of multiple targets of a specifi c pathway. In this review, we describe the metabolic reprogramming associated to cancer, with a special interest in the altered lipid metabolism. Next, we describe specifi c 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. metabolism is interrupted, they may rely on glucose-dependent anaplerosis of the TCA cycle ( 11 ). This...

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“…to inhibit translation (11,12). miRNAs regulate cellular homeostasis and development and also several processes involved in tumorigenesis (12)(13)(14). The reported cross-talk between miRNAs and several lipid metabolism processes, like lipogenesis, lipolysis, or lipophagy (13), could contribute to their action as tumor suppressors or as oncomiRNAs.…”

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