miR-696 plays a role in hepatic gluconeogenesis in ob/ob mice by targeting PGC-1α
miR-696 plays a role in hepatic gluconeogenesis in ob/ob mice by targeting PGC-1α
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DOI：
10.3892/ijmm.2016.2659
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发表时间：
2016-09-01
影响因子：
5.4
通讯作者：
Xiang, Yang
中科院分区：
文献类型：
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作者：
Fang, Zhijuan;Li, Peng;Xiang, Yang
已知微小RNA（miRNAs或miRs）在2型糖尿病中起重要作用，并且过氧化物酶体增殖物激活受体-γ（PPARgamma）共激活因子-1 α（PGC-1 α）参与肝胰岛素抵抗的发病机制。然而，PGC-1 alpha和miRNAs在疾病中的相关性（如果有的话）尚未确定。因此，在本研究中，我们的目的是检查PGC-1 α和miRNA在糖尿病中的相关性。为此，我们使用了从C57 BL/6小鼠和ob/ob小鼠分离的原代肝细胞。首先，我们发现体内miR-696和PGC-1 α蛋白水平之间呈负相关。其次，体外证据表明，用pre-miR-696-LV感染显著降低了PGC-1 α表达，而用anti-miR-696-LV感染则增加了PGC-1 α蛋白水平。第三，荧光素酶报告基因测定证实miR-696直接识别PGC-1 α转录物3 '非翻译区内的特定位置。此外，miR-696靶向PGC-1 α的生物学后果通过测量特征性肝促凋亡酶PEPCK的表达水平来确定，PEPCK在肝脏中通过转录因子的共激活由PGC-1 α调节。综上所述，我们的研究结果表明，miR-696通过抑制肝脏中PGC-1 α的翻译，在肝脏肿瘤发生和胰岛素抵抗的发展中起着重要作用。
MicroRNAs (miRNAs or miRs) are known to play a vital role in type 2 diabetes, and peroxisome proliferator-activated receptor-gamma (PPAR gamma) coactivator-1 alpha (PGC-1 alpha) is involved in the pathogenesis of hepatic insulin resistance. However, the correlation, if any, between PGC-1 alpha and miRNAs in the disease has not yet been determined. Thus, in the present study, we aimed to examine the correlation between PGC-1 alpha and miRNAs in diabetes. For this purpose, we used primary hepatocytes isolated from C57BL/6 mice and ob/ob mice. First, we found an inverse correlation between miR-696 and PGC-1 alpha protein levels in vivo. Second, in vitro evidence demonstrated that PGC-1 alpha expression was significantly decreased by infection with pre-miR-696-LV, whereas infection with anti-miR-696-LV increased the PGC-1 alpha protein levels. Third, a luciferase reporter assay confirmed that miR-696 directly recognizes a specific location within the 3'-untranslated region of PGC-1 alpha transcripts. Furthermore, the biological consequences of miR-696 targeting PGC-1 alpha were determined by measuring the expression levels of the characteristic hepatic gluconeogenic enzyme, PEPCK, which is regulated by PGC-1 alpha in the liver via the coactivation of transcription factors. Taken together, our findings demonstrate that miR-696 plays an important role in the development of hepatic gluconeogenesis and insulin resistance through the inhibition of PGC-1 alpha translation in the liver.