Selenium-sensitive miRNA-181a-5p targeting SBP2 regulates selenoproteins expression in cartilage.
Selenium-sensitive miRNA-181a-5p targeting SBP2 regulates selenoproteins expression in cartilage.
复制标题
靶向 SBP2 的硒敏感 miRNA-181a-5p 调节软骨中的硒蛋白表达
DOI：
10.1111/jcmm.13858
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发表时间：
2018-12
影响因子：
5.3
通讯作者：
Lu S
中科院分区：
文献类型：
--
作者：
Min Z;Guo Y;Sun M;Hussain S;Zhao Y;Guo D;Huang H;Heng L;Zhang F;Ning Q;Han Y;Xu P;Zhong N;Sun J;Lu S
硒（Se）缺乏导致几种硒蛋白的生物合成缺陷，并与异常软骨发生有关。硒代半胱氨酸插入序列（SECIS）与SECIS结合蛋白2（SBP2）的相互作用是硒与硒蛋白代谢平衡的关键环节。Gpx1、Gpx4和SelS与细胞内的SBP 2具有不同的结合亲和力。根据我们的结果，miR-181 a-5p和SBP 2似乎都是硒敏感的，并且在硒充足的环境下调节C28/I2细胞中硒蛋白的表达。而在缺硒大鼠软骨和SeD C28/I2细胞中的表达趋势则相反。通过报告基因和脱靶实验确定，SBP2是C28/I2细胞中miR-181a-5p的直接靶基因。miR-181 a-5p可调控C28/I2细胞内的SBP2和硒蛋白。根据硒供应水平的不同，将C28/I2细胞分为正常硒、硒缺乏和硒硫三组，经过7天的缺硒过程，然后在所有组中敲低并过表达SBP 2。此外，所选硒蛋白在第二代低硒饮食大鼠软骨中下调。硒缺乏可导致硒蛋白表达下降，而硒蛋白的表达依赖于硒敏感的miR-181 a-5p在转录后水平参与调控SBP2。它涉及一系列抗氧化和ECM（细胞外基质）基因，以克服ROS相关的压力，保护基本的生理功能，并维持软骨的弹性和弹性之间的平衡。
Selenium (Se) deficiency brings about defects in the biosynthesis of several selenoproteins and has been associated with aberrant chondrogenesis. Selenocysteine (Sec) Insertion Sequence (SECIS) and SECIS binding protein 2 (SBP2) interaction is a very critical node for the metabolic balance between Se and selenoproteins. The Gpx1, Gpx4 and SelS have different binding affinities with SBP2 in cells. According to our results, both miR‐181a‐5p and SBP2 appeared to be selenium‐sensitive and regulated the expression of selenoproteins in C28/I2 cells under Se sufficient environment. However, they showed significantly opposite expression trend in Se deficiency rats cartilage and SeD C28/I2 cells. The SBP2 is a direct target gene of miR‐181a‐5p in C28/I2 cells as determined by reporter gene and off‐target experiments. And the miR‐181a‐5p could regulate SBP2 and the selenoproteins in C28/I2 cells. Depending upon the Se supply levels, C28/I2 cells were divided into three groups, that is normal Se, SeD and SeS, which underwent through a 7‐day Se deprivation process, then SBP2 was knocked‐down and overexpressed in all the groups. Moreover, the selected selenoproteins were down‐regulated in second‐generation low Se diet rat cartilage. The selenoproteins expression was decreased by Se deficiency which depended on the Selenium‐sensitive miR‐181a‐5p to participate and regulate SBP2 at post‐transcriptional level. It involves a series of antioxidant and ECM (extracellular matrix) genes, to overcome the ROS‐related stress for the protection of essential physiological functions and to maintain the balance between anabolism and catabolism of the cartilage.
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影响因子：
4.5
作者：
Downey CM;Horton CR;Carlson BA;Parsons TE;Hatfield DL;Hallgrímsson B;Jirik FR
通讯作者：
Jirik FR
影响因子：
14.9
作者：
Takeuchi A;Schmitt D;Chapple C;Babaylova E;Karpova G;Guigo R;Krol A;Allmang C
通讯作者：
Allmang C
影响因子：
56.9
作者：
Kryukov, GV;Castellano, S;Gladyshev, VN
通讯作者：
Gladyshev, VN
影响因子：
7
作者：
Cao, J.;Li, S.;Caterson, B.
通讯作者：
Caterson, B.
影响因子：
4.8
作者：
Anestål, K;Arnér, ESJ
通讯作者：
Arnér, ESJ