Non-Coding and Regulatory RNAs as Epigenetic Remodelers of Fatty Acid Homeostasis in Cancer

SIMPLE SUMMARY: Reprogramming of energy metabolism is an emerging hallmark of cancer development. Progression in a tumor cell requires new biogenesis of fatty acids (FA) for membrane synthesis, as signaling molecules or as energy input. Here, we provide a review of fatty acid metabolism misbalance from a cancer perspective (lipids’ storage formation, their hydrolysis, extra FAs uptake, FA synthesis, FA oxidation, and finally, FA activation and desaturation) and we summarize the reported non-coding RNAs affecting these processes as new strategies to target fatty acid availability in cancer cells. ABSTRACT: Cancer cells commonly display metabolic fluctuations. Together with the Warburg effect and the increased glutaminolysis, alterations in lipid metabolism homeostasis have been recognized as a hallmark of cancer. Highly proliferative cancer cells upregulate de novo synthesis of fatty acids (FAs) which are required to support tumor progression by exerting multiple roles including structural cell membrane composition, regulators of the intracellular redox homeostasis, ATP synthesis, intracellular cell signaling molecules, and extracellular mediators of the tumor microenvironment. Epigenetic modifications have been shown to play a crucial role in human development, but also in the initiation and progression of complex diseases. The study of epigenetic processes could help to design new integral strategies for the prevention and treatment of metabolic disorders including cancer. Herein, we first describe the main altered intracellular fatty acid processes to support cancer initiation and progression. Next, we focus on the most important regulatory and non-coding RNAs (small noncoding RNA—sncRNAs—long non-coding RNAs—lncRNAs—and other regulatory RNAs) which may target the altered fatty acids pathway in cancer.