MicroRNA 33a-5p (miR-33a-5p)

MicroRNA 33a-5p (miR-33a-5p) is a highly conserved, small non-coding RNA that plays a central role in the regulation of lipid and glucose metabolism (PubMed: 20466932). It is located within the intronic sequence of the SREBF2 gene, a master regulator of cholesterol synthesis, and acts to coordinately control cellular cholesterol levels by inhibiting the expression of the ATP-binding cassette transporter A1 (ABCA1) (PubMed: 20466928). By suppressing ABCA1, miR-33a-5p reduces cholesterol efflux to apolipoprotein A-I, thereby lowering high-density lipoprotein (HDL) levels and promoting atherogenesis (Science: 10.1126/science.1189862). Beyond its metabolic functions, miR-33a-5p is involved in regulating the cell cycle, apoptosis, and inflammatory responses, often acting as a tumor suppressor in various malignancies by targeting oncogenes like MYC and CDK6 (PubMed: 25633789). Therapeutic targeting of miR-33a-5p primarily involves the use of antisense oligonucleotides, such as antagomirs or locked nucleic acids (LNAs), to derepress its target genes and treat cardiovascular and metabolic diseases (Journal of Clinical Investigation: 10.1172/JCI43799). Clinical candidates like RG-125 (AZD4076) have been investigated for their ability to improve lipid profiles and treat non-alcoholic steatohepatitis (NASH) (ClinicalTrials.gov: NCT02612662).

Other names

hsa-miR-33a-5pmiR-33aMIR33AMicroRNA 33a

Antisense inhibition of microRNA to derepress target gene expression (e.g., ABCA1)