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MicroRNA-33 regulates sterol regulatory element-binding protein 1 expression in mice

2013; Nature Portfolio; Volume: 4; Issue: 1 Linguagem: Inglês

10.1038/ncomms3883

2041-1723

Takahiro Horie, Tomohiro Nishino, Osamu Baba, Yasuhide Kuwabara, Tetsushi Nakao, Masataka Nishiga, Shunsuke Usami, Masayasu Izuhara, Naoya Sowa, Naoya Yahagi, Hitoshi Shimano, Shigenobu Matsumura, Kazuo Inoue, Hiroyuki Marusawa, Tomoyuki Nakamura, Koji Hasegawa, Noriaki Kume, Masayuki Yokode, Toru Kita, Takeshi Kimura, Koh Ono,

Cancer, Lipids, and Metabolism

Abstract MicroRNAs (miRs) are small non-protein-coding RNAs that bind to specific mRNAs and inhibit translation or promote mRNA degradation. Recent reports have indicated that miR-33, which is located within the intron of sterol regulatory element-binding protein (SREBP) 2, controls cholesterol homoeostasis and may be a potential therapeutic target for the treatment of atherosclerosis. Here we show that deletion of miR-33 results in marked worsening of high-fat diet-induced obesity and liver steatosis. Using miR-33 −/− Srebf1 +/− mice, we demonstrate that SREBP-1 is a target of miR-33 and that the mechanisms leading to obesity and liver steatosis in miR-33 −/− mice involve enhanced expression of SREBP-1. These results elucidate a novel interaction between SREBP-1 and SREBP-2 mediated by miR-33 in vivo .