MicroRNA-378 regulates adiponectin expression in adipose tissue: a new plausible mechanism.
MicroRNA-378 regulates adiponectin expression in adipose tissue: a new plausible mechanism.
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DOI：
10.1371/journal.pone.0111537
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Sata M
中科院分区：
文献类型：
--
作者：
Ishida M;Shimabukuro M;Yagi S;Nishimoto S;Kozuka C;Fukuda D;Soeki T;Masuzaki H;Tsutsui M;Sata M
调节脂联素表达的机制尚未完全阐明。microRNAs（miRNAs）是一种调节基因表达的非编码小分子RNA，参与肥胖和胰岛素抵抗等生物学过程。我们评估了miRNA-378通路是否参与调节脂联素的表达。首先，我们通过计算机分析确定了脂联素基因3 '非翻译区（3' UTR）中miRNA-378的推定靶位点。在过表达miRNA-378模拟物的3 T3-L1细胞中，脂联素mRNA和蛋白水平降低。通过过表达miRNA-378的模拟物来抑制表达海肾荧光素酶-脂联素-3 'UTR序列的HEK 293 T细胞中的发光活性，并且通过添加miRNA-378的抑制剂来逆转该降低。此外，我们证实了模拟物的抑制作用在miR-378 3′-UTR结合位点的缺失突变体中被取消。加入肿瘤坏死因子-α（TNFα）可导致3 T3-L1细胞中miR-378在mRNA和蛋白水平上调，脂联素在mRNA和蛋白水平下调。与正常C57 BL/6小鼠相比，糖尿病ob/ob小鼠中miR-378水平较高，脂联素mRNA水平较低，miR-378和脂联素水平呈良好负相关（r =-0.624，p = 0.004）。 我们发现miRNA-378的水平可以通过3 'UTR序列结合位点调节脂联素的表达。我们的研究结果证明了miRNAs在调节脂联素表达中的作用。
Mechanisms regulating adiponectin expression have not been fully clarified. MicroRNAs (miRNAs), small non-coding RNAs that regulate gene expression, are involved in biological processes, including obesity and insulin resistance. We evaluated whether the miRNA-378 pathway is involved in regulating adiponectin expression. First, we determined a putative target site for miRNA-378 in the 3 prime untranslated region (3'UTR) of the adiponectin gene by in silico analysis. The levels of adiponectin mRNA and protein were decreased in 3T3-L1 cells overexpressing the mimic of miRNA-378. Luminescence activity in HEK293T cells expressing a renilla-luciferase-adiponectin-3'UTR sequence was inhibited by overexpressing the mimic of miRNA-378, and the decrease was reversed by adding the inhibitor of miRNA-378. Moreover, we confirmed the inhibitory effects of the mimic were cancelled in a deleted mutant of the miR-378 3′-UTR binding site. Addition of tumor necrosis factor-α (TNFα) led a upregulation of miR-378 and downregulation of adiponectin at mRNA and protein levels in 3T3-L1 cells. Level of miR-378 was higher and mRNA level of adiponectin was lower in diabetic ob/ob mice than those of normal C57BL/6 mice and levels of miR378 and adiponectin were negatively well correlated (r = −0.624, p = 0.004). We found that levels of miRNA-378 could modulate adiponectin expression via the 3'UTR sequence-binding site. Our findings warrant further investigations into the role of miRNAs in regulating the adiponectin expression.
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影响因子：
3.7
作者：
Rantalainen M;Herrera BM;Nicholson G;Bowden R;Wills QF;Min JL;Neville MJ;Barrett A;Allen M;Rayner NW;Fleckner J;McCarthy MI;Zondervan KT;Karpe F;Holmes CC;Lindgren CM
通讯作者：
Lindgren CM
影响因子：
7.7
作者：
Xie H;Lim B;Lodish HF
通讯作者：
Lodish HF
炎症和代谢疾病中的脂肪因子。
DOI：
10.1038/nri2921
发表时间：
2011-02
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
2.8
作者：
Kang, Min;Yan, Li-Mei;Ou, He-Sheng
通讯作者：
Ou, He-Sheng
影响因子：
29
作者：
Eichner, Lillian J.;Perry, Marie-Claude;Giguere, Vincent
通讯作者：
Giguere, Vincent