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

机译:长非编码RNA MIAT在晶状体上皮细胞增殖,凋亡和迁移中的作用:临床和体外研究

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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.
机译:与年龄有关的白内障是最常见的衰老慢性疾病之一,并且是世界领先的致盲性疾病。长的非编码RNA在几种生物学过程和复杂疾病中起重要作用。但是,lncRNA在白内障中的作用仍然未知。在这里,我们从透明的和年龄匹配的白内障晶状体中提取总RNA,并使用微阵列分析确定了lncRNA表达谱。我们发现38 lncRNA在透明和白内障晶状体之间差异表达。通过定量RT-PCR进一步验证了20种差异表达的lncRNA中的17种。在全血和白内障患者的房水中,一种最丰富的lncRNA MIAT被特别上调。 MIAT基因敲低可能会影响氧化应激后人晶状体上皮细胞(HLEC)的增殖,凋亡和迁移。后囊混浊(PCO)是白内障手术的常见并发症,与发炎因子的异常产生有关。 MIAT基因敲低可以抑制肿瘤坏死因子-α诱导的HLEC异常增殖和迁移,提示MIAT在PCO相关病理过程中具有潜在作用。此外,我们发现MIAT充当ceRNA,并与Akt和miR-150-5p形成反馈环来调节HLEC功能。总的来说,这项研究为年龄相关性白内障的发病机理提供了新颖的见解。

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