Dynamic and differential regulation in the microRNA expression in the developing and mature cataractous rat lens.
Dynamic and differential regulation in the microRNA expression in the developing and mature cataractous rat lens.
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DOI：
10.1111/jcmm.12094
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发表时间：
2013-09
影响因子：
5.3
通讯作者：
Singh DP
中科院分区：
文献类型：
--
作者：
Kubo E;Hasanova N;Sasaki H;Singh DP
最近的证据支持microRNAs(MiRNAs)在调节基因表达方面的作用，并且已知基因表达的变化会影响参与衰老疾病发展的细胞。利用发育中的大鼠晶状体上皮细胞(LECs)，我们通过基于微阵列的方法对miRNAs的表达进行了分析。很少有已知参与发病或细胞保护的基因表达变化受到miRNA表达的唯一影响。在晶状体上皮细胞和晶状体中，大多数miRNAs的丰度(let 7b、let 7c、miR29a、miR29c、miR126和miR551b)在胚胎晚期、出生后和白内障中增加或减少。其中，Shumiya白内障大鼠(SCR)白内障晶状体上皮细胞中miR29a、miR29c和miR126的表达显著降低。具体地说，细胞骨架重塑基因原肌球蛋白(TM)1α和2β是miR29c的靶标，并被抑制剂实验证明是过度刺激的，它们与病理生理学的启动有关。在转染实验中，提高miR29c的表达水平会导致Tm1α和2β的表达相应降低，提示miR29c可能调节Tm1α和2β的翻译。在转基因的小鼠晶状体上皮细胞中，Tm1α的3‘UTR型荧光素酶活性显著降低，而不是2β。这些发现证明了miRNAs表达的变化，靶分子有可能作为衰老的诊断指标，并作为基于miR的治疗年龄相关疾病的基础。
Recent evidence supports a role for microRNAs (miRNAs) in regulating gene expression, and alterations in gene expression are known to affect cells involved in the development of ageing disorders. Using developing rat lens epithelial cells (LECs), we profiled the expression of miRNAs by a microarray-based approach. Few gene expression changes known to be involved in pathogenesis or cytoprotection were uniquely influenced by miRNA expression. Most miRNAs increased or decreased in abundance (let 7b, let 7c, miR29a, miR29c, miR126 and miR551b) in LECs/lenses during late embryonic and post-natal development and in cataract. Among them, miR29a, miR29c and miR126 were dramatically decreased in cataractous LECs from Shumiya Cataract Rats (SCRs). Specifically, the cytoskeleton remodelling genes tropomyosin (Tm) 1α and 2β, which have been implicated in the initiation of pathophysiology, were targets of miR29c and were over-stimulated as demonstrated by inhibitor experiments. In transfection experiments, increasing the level of miR29c caused a corresponding decrease in the expression of Tm1α and 2β, suggesting that miR29c may regulate the translation of Tm1α and 2β. 3′UTR luciferase activity of Tm1α, not 2β, was significantly decreased in miR29c-transfected mouse LECs. These findings demonstrate changes in miRNAs expression, and target molecules have potential as diagnostic indicators of ageing and as a foundation of miR-based therapeutics for age-related diseases.
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影响因子：
64.5
作者：
Budovskaya YV;Wu K;Southworth LK;Jiang M;Tedesco P;Johnson TE;Kim SK
通讯作者：
Kim SK
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Singh DP
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通讯作者：
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