MiR-33 connects cholesterol to the cell cycle

MicroRnAs (miRnAs) are non-coding RnAs that downregulate gene expression at the post-transcriptional level. in recent years, their regulatory roles have been receiving much attention. MiR33 is one such miRnA, recently identified as a critical regulator of cholesterol homeostasis1 and insulin signaling.2 The recent study by Cirera-salinas et al.3 described a new role of miR33 for the regulation of cell cycle progression and cell proliferation. in a previous study, Fernandez-Hernando, the senior author of the current paper, and Moore1 determined that miR33 is an intronic miRnA located within the gene encoding sterol-regulatory element-binding protein-2 (sReBP-2), the key transcriptional factor for cholesterol biosynthesis and transport. MiR33 inhibits high-density lipoprotein biogenesis in the liver and cellular cholesterol efflux.1 since sReBPs have also been implicated in the regulation of cell cycle,4–6 the authors investigated the link between miR33 and cell cycle progression as well as cell proliferation.3 Using bioinformatic approaches, the authors predicted potential miR33 target genes involved in cell cycle progression and cell proliferation.3 Among these predicted genes, they found that overexpression of miR33 inhibits cyclin-dependent kinase 6 (CDK6) and cyclin D1 (CCnD1) mRnA expression and reduces cell proliferation. Conversely, inhibiting miR33 increases mRnA expression of CDK6 and cyclin D1 and promotes cell proliferation. Further, the authors found that the level of endogenous miR33 is inversely correlated with the levels of CDK6 and CCnD1. endogenous miR33 levels decreased upon cells’ release from mitosis and increased thereafter, whereas CDK6 and CCnD1 levels first rose and then declined. Furthermore, miR33 arrested the cell Cell Cycle News & Views