Regulation of cholesterol biosynthesis and lipid metabolism: A microRNA management perspective

Cellular disruption of lipid and cholesterol metabolism results in pathological processes linked to metabolic and cardiovascular diseases. Classically, at the transcription stages, the Cholesterol levels are controlled by two cellular pathways. First, the SREBP transcription factor family controls Cholesterol biosynthesis via transcriptional regulation of critical rate-limiting cholesterogenic and lipogenic proteins. Secondly, The LXR/RXR transcription factor family controls cholesterol shuttling via transcriptional regulation of cholesterol transport proteins. In addition, the posttranscriptional control of gene expression of various enzymes and proteins of cholesterol biosynthesis pathways is mediated by small non-coding microRNAs. Regulatory noncoding miRNAs are critical regulators of biological processes, including developmental and metabolic functions. miRNAs function to fine-tune lipid and cholesterol metabolism pathways by controlling the mRNA levels and translation of critical molecules in each pathway. This review discusses the regulatory roles of miRNAs in cholesterol and lipid metabolism via direct and indirect effects on their target genes, including SREBP, LXR, HDL, LDL, and ABCA transporters. We also discuss the therapeutic implications of miRNA functions and their purported role in the potentiation of small molecule therapies.