| First Author | Najafi-Shoushtari SH | Year | 2010 |
| Journal | Science | Volume | 328 |
| Issue | 5985 | Pages | 1566-9 |
| PubMed ID | 20466882 | Mgi Jnum | J:160972 |
| Mgi Id | MGI:4456895 | Doi | 10.1126/science.1189123 |
| Citation | Najafi-Shoushtari SH, et al. (2010) MicroRNA-33 and the SREBP host genes cooperate to control cholesterol homeostasis. Science 328(5985):1566-9 |
| abstractText | Proper coordination of cholesterol biosynthesis and trafficking is essential to human health. The sterol regulatory element-binding proteins (SREBPs) are key transcription regulators of genes involved in cholesterol biosynthesis and uptake. We show here that microRNAs (miR-33a/b) embedded within introns of the SREBP genes target the adenosine triphosphate-binding cassette transporter A1 (ABCA1), an important regulator of high-density lipoprotein (HDL) synthesis and reverse cholesterol transport, for posttranscriptional repression. Antisense inhibition of miR-33 in mouse and human cell lines causes up-regulation of ABCA1 expression and increased cholesterol efflux, and injection of mice on a western-type diet with locked nucleic acid-antisense oligonucleotides results in elevated plasma HDL. Our findings indicate that miR-33 acts in concert with the SREBP host genes to control cholesterol homeostasis and suggest that miR-33 may represent a therapeutic target for ameliorating cardiometabolic diseases. |
