microrna 223 coordinates cholesterol homeostasis

• DOI: 10.17615/jy7z-sa61
• Publication Date: 2014-09-22
• Authors: Michael G. Levin; Kasey C. Vickers; Kasey C. Vickers; Brian T. Palmisano; Ronald C. Taylor; Landstreet; Alan T. Remaley; Cynthia L. Toth; Praveen Sethupathy; Bassem M. Shoucri; HL Cui; Kerry-Anne Rye; Fatiha Tabet
• Keywords: Mice, Knockout; 0301 basic medicine; Models, Genetic; Reverse Transcriptase Polymerase Chain Reaction; Cholesterol, HDL; 3. Good health; MicroRNAs; 03 medical and health sciences; Cholesterol; HEK293 Cells; Liver; Cell Line, Tumor; Animals; Homeostasis; Humans; Transcriptome; Cells, Cultured; Oligonucleotide Array Sequence Analysis

Significance Results from this study represent a breakthrough in our understanding of posttranscriptional control of cholesterol metabolism and how microRNAs (miRNAs) are at the heart of cholesterol regulatory circuitry and homeostasis. Although cells are adept at maintaining proper cholesterol levels, it was unknown how cells posttranscriptionally coordinate cholesterol uptake, efflux, and synthesis. MicroRNA-223 (miR-223) transcription and expression are maintained by cholesterol, and, as a feedback network, miR-223 inhibits cholesterol biosynthesis and uptake and increases cholesterol efflux. This study clearly demonstrates the extensive role that miRNAs play in coordinating metabolic adaptation to disease and general homeostasis. This work highlights a unique regulatory control point for cholesterol homeostasis and illustrates how important the study of miRNAs is to the greater understanding of dyslipidemia and cardiovascular disease.