Ultracnnserved element uc.333 increases insulin sensitivity by binding to miR-223
Ultracnnserved element uc.333 increases insulin sensitivity by binding to miR-223
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超保守元件 uc.333 通过与 miR-223 结合增加胰岛素敏感性
DOI：
10.18632/aging.103020
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发表时间：
2020-04-30
期刊：
影响因子：
5.2
通讯作者：
Li, Jian
中科院分区：
文献类型：
--
作者：
Zhang, Yang;Sun, Jingyu;Li, Jian
胰岛素抵抗（IR）导致糖尿病和衰老。超保守元件（UCE）是一类在人类、小鼠和大鼠中100%保守的长链非编码RNA（lncRNA）。我们使用lncRNA微阵列鉴定lncRNA uc.333，然后使用定量实时聚合酶链反应分析其在非酒精性脂肪肝病（NAFLD）患者、db/db小鼠、高脂饮食喂养小鼠、IL-6治疗小鼠和TNF-α治疗小鼠肝脏中的表达。采用荧光原位杂交、Western blot和miRNA微阵列分析研究uc.333在IR中的潜在机制。结果显示，在NAFLD患者和治疗小鼠的肝组织中，uc.333表达降低。此外，uc.333的过表达降低了IR，而敲低uc.333则增加了IR。我们还证实了uc.333与miR-223结合，并且miR-223的水平在患者和治疗小鼠的肝脏中增加。这些发现表明，uc.333通过与miR-223结合改善IR;因此，uc.333可能是治疗和预防IR的有用靶点。
Insulin resistance (IR) contributes to diabetes and aging. Ultraconserved elements (UCEs) are a class of long noncoding RNAs (lncRNAs) that are 100% conserved in humans, mice, and rats. We identified the lncRNA uc.333 using an lncRNA microarray and then used quantitative real-time polymerase chain reaction to analyze its expression in the livers of nonalcoholic fatty liver disease (NAFLD) patients, db/db mice, high-fat diet–fed mice, IL-6-treated mice, and TNF-α-treated mice. The underlying mechanisms of uc.333 in IR were investigated using fluorescence in situ hybridization, Western blot, and miRNA microarray analyses. The results revealed that uc.333 expression was decreased in liver tissues from NAFLD patients and treated mice. Furthermore, overexpression of uc.333 decreased IR, whereas knocking down uc.333 increased IR. We also confirmed that uc.333 binds to miR-223 and that the levels of miR-223 were increased in the livers of patients and treated mice. These findings showed that uc.333 improves IR by binding to miR-223; thus, uc.333 may be a useful target for the treatment and prevention of IR.