Identification of microRNA that represses IRS-1 expression in liver.
Identification of microRNA that represses IRS-1 expression in liver.
复制标题
抑制肝脏中IRS-1表达的microRNA鉴定。
DOI：
10.1371/journal.pone.0191553
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Araki E
中科院分区：
文献类型：
--
作者：
Ono K;Igata M;Kondo T;Kitano S;Takaki Y;Hanatani S;Sakaguchi M;Goto R;Senokuchi T;Kawashima J;Furukawa N;Motoshima H;Araki E
microRNA（miRNAs）是一种短的非编码RNA，在转录后调节基因表达，参与几乎所有的细胞过程。最近有几种miRNAs与葡萄糖代谢有关，但miRNAs在胰岛素抵抗性疾病（如肥胖或2型糖尿病）中的作用在很大程度上是未知的。在此，我们关注miR-222，其表达在注射金硫代葡萄糖（G+HFHSD）的高脂肪/高蔗糖饮食喂养的小鼠的肝脏中增加。原代小鼠肝细胞中miR-222的过表达减弱了胰岛素诱导的Akt磷酸化，表明miR-222负调节胰岛素信号传导。根据计算机模拟分析，miR-222可能与IRS-1基因的3′非翻译区（3′ UTR）结合，IRS-1基因是一种关键的胰岛素信号分子。事实上，IRS-1蛋白表达在G+HFHSD-fed小鼠的肝脏中降低。我们通过荧光素酶分析进一步证实了miR-222与IRS-1的3′ UTR之间的直接相互作用。我们的研究结果表明，上调miR-222，随后降低IRS-1的表达可能是一个可行的机制，胰岛素抵抗的肝脏。
MicroRNAs (miRNAs) are short, non-coding RNAs that post-transcriptionally regulate gene expression and have been shown to participate in almost every cellular process. Several miRNAs have recently been implicated in glucose metabolism, but the roles of miRNAs in insulin-resistant conditions, such as obesity or type 2 diabetes, are largely unknown. Herein, we focused on miR-222, the expression of which was increased in the livers of high fat/high sucrose diet-fed mice injected with gold thioglucose (G+HFHSD). Overexpression of miR-222 in primary mouse hepatocytes attenuated Akt phosphorylation induced by insulin, indicating that miR-222 negatively regulates insulin signaling. As per in silico analysis, miR-222 potentially binds to the 3′ untranslated region (3′ UTR) of the IRS-1 gene, a key insulin signaling molecule. In fact, IRS-1 protein expression was decreased in the livers of G+HFHSD-fed mice. We further confirmed a direct interaction between miR-222 and the 3′ UTR of IRS-1 via luciferase assays. Our findings suggest that up-regulation of miR-222 followed by reduction in IRS-1 expression may be a viable mechanism of insulin resistance in the liver.
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影响因子：
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