Role of long non-coding RNA MIAT in proliferation, apoptosis and migration of lens epithelial cells: a clinical and in vitro study.

Role of long non-coding RNA MIAT in proliferation, apoptosis and migration of lens epithelial cells: a clinical and in vitro study.
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DOI:
10.1111/jcmm.12755
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发表时间:
2016-03
影响因子:
5.3
通讯作者:
Yan B
Yan B
中科院分区:
医学2区
文献类型:
--
作者:
Shen Y;Dong LF;Zhou RM;Yao J;Song YC;Yang H;Jiang Q;Yan B

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与年龄相关的白内障是最常见的衰老慢性疾病之一,也是世界上主要的致盲疾病。长链非编码rna在多种生物学过程和复杂疾病中发挥着重要作用。然而,lncrna在白内障发病中的作用尚不清楚。在这里,我们从透明和年龄匹配的人白内障晶状体中提取总rna,并使用微阵列分析确定lncRNA表达谱。我们发现38个lncrna在透明晶状体和白内障晶状体之间存在差异表达。20个差异表达的lncrna中有17个通过定量RT - pcr进一步验证。其中最丰富的lncRNA MIAT在白内障患者的全血血浆和房水中均被特异性上调。MIAT基因敲低可影响氧化应激下人晶状体上皮细胞(HLECs)的增殖、凋亡和迁移。后囊膜混浊(PCO)是白内障手术中一种常见的并发症,它与炎症因子的异常产生有关。MIAT敲低可抑制肿瘤坏死因子α诱导的HLECs异常增殖和迁移,提示MIAT在PCO相关病理过程中可能发挥作用。此外,我们发现MIAT作为ceRNA,与Akt和miR‐150‐5p形成反馈回路,调节HLEC功能。总的来说,这项研究为年龄相关性白内障的发病机制提供了新的见解。
Age‐related cataract is among the most common chronic disorders of ageing and is the world's leading blinding disorder. Long non‐coding RNAs play important roles in several biological processes and complicated diseases. However, the role of lncRNAs in the setting of cataract is still unknown. Here, we extracted total RNAs from the transparent and age‐matched cataractous human lenses, and determined lncRNA expression profiles using microarray analysis. We found that 38 lncRNAs were differentially expressed between transparent and cataractous lenses. 17 of 20 differentially expressed lncRNAs were further verified by quantitative RT‐PCRs. One top abundant lncRNA, MIAT, was specifically up‐regulated both in the plasma fraction of whole blood and aqueous humor of cataract patients. MIAT knockdown could affect the proliferation, apoptosis and migration of Human lens epithelial cells (HLECs) upon oxidative stress. Posterior capsule opacification (PCO) is a common complication of cataract surgery, which is associated with abnormal production of inflammatory factors. MIAT knockdown could repress tumour necrosis factor‐α‐induced abnormal proliferation and migration of HLECs, suggesting a potential role of MIAT in PCO‐related pathological process. Moreover, we found that MIAT acted as a ceRNA, and formed a feedback loop with Akt and miR‐150‐5p to regulate HLEC function. Collectively, this study provides a novel insight into the pathogenesis of age‐related cataract.