LncRNA GAS5 regulates migration and epithelial-to-mesenchymal transition in lens epithelial cells via the miR-204-3p/TGFBR1 axis
LncRNA GAS5 regulates migration and epithelial-to-mesenchymal transition in lens epithelial cells via the miR-204-3p/TGFBR1 axis
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DOI：
10.1038/s41374-021-00713-3
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发表时间：
2021-12-16
影响因子：
5
通讯作者：
Zheng, Guangying
中科院分区：
文献类型：
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作者：
Li, Xiao;Sun, Miaomiao;Zheng, Guangying
糖尿病性白内障（DC）是继发于糖尿病的主要眼部并发症。晶状体上皮细胞（LECs）的上皮-间质转化（EMT）是DC进展中的一个重要事件。长链非编码rna （lncrna）和microrna参与了各种生物过程和疾病。本研究的目的是探讨lncRNA生长抑制特异性转录物5 （GAS5）和microRNA-204-3p （miR-204-3p）失调在高糖（HG）刺激的LECs发病机制中的作用。结果显示，与对照组相比，DC患者和hg处理的LECs前晶状体囊组织中GAS5上调，而miR-204-3p下调。功能实验表明，慢病毒介导的GAS5缺失以及miR-204-3p的过表达抑制了hg处理的LECs的迁移和EMT。进一步的机制研究表明，lncRNA GAS5/miR-204-3p/type 1 receptor of transforming growth factor-beta （TGFBR1）在这一过程中具有调控作用。总的来说，我们证明了GAS5的失调通过miR-204-3p/TGFBR1轴影响HG条件下晶状体上皮细胞的迁移和EMT。目前的研究结果可能为研究DC发生的分子机制提供新的见解。在高糖条件下，LECs获得了间充质细胞的特性，如高迁移能力和侵袭性，这是DC进展的基础。作者证明，lncRNA GAS5通过调节miR-204-3p/TGFBR1轴促进高糖诱导的晶状体上皮细胞迁移和上皮向间质转化。因此，这项研究为DCs的发病机制提供了新的见解。
Diabetic cataract (DC) is a major ocular complication secondary to diabetes mellitus. The epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs) is an important event in DC progression. Long non-coding RNAs (lncRNAs) and microRNAs are involved in various biological processes and disorders. The aim of this study was to investigate the roles of lncRNA growth arrest-specific transcript 5 (GAS5) and microRNA-204-3p (miR-204-3p) deregulation in the pathogenic mechanism of high glucose (HG)-stimulated LECs. The results show that GAS5 was up-regulated, whereas miR-204-3p was down-regulated in anterior lens capsule tissues of DC patients and in HG-treated LECs compared to their controls, respectively. Functional experiments suggest that the lentivirus-mediated depletion of GAS5, as well as overexpression of miR-204-3p, suppressed migration and EMT in HG-treated LECs. Further mechanistic studies revealed that lncRNA GAS5/miR-204-3p/type 1 receptor of transforming growth factor-beta (TGFBR1) has a regulatory role in the process. Collectively, we demonstrated that dysregulation of GAS5 affects lens epithelial cell migration and EMT under HG conditions via the miR-204-3p/TGFBR1 axis. The current findings may provide new insights into the molecular mechanisms of DC development.Under high-glucose conditions, LECs obtain characteristics of mesenchymal cells such as high migratory capacity and invasiveness, which is the foundational basis for DC progression. The authors demonstrated that lncRNA GAS5 facilitates high glucose-induced lens epithelial cell migration and epithelial-to-mesenchymal transition by regulating the miR-204-3p/TGFBR1 axis. This study, therefore, provides novel insights into the pathogenesis of DCs.