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Role of lncRNA NEAT1 mediated by YY1 in the development of diabetic cataract via targeting the microRNA-205-3p/MMP16 axis

机译:LNCRNA Neat1的作用在YY1中介导的糖尿病白内障通过靶向MicroRNA-205-3P / MMP16轴的发育

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OBJECTIVE: We aimed at investigating the possible role and mechanism of NEAT1 in the pathogenesis of diabetic cataract. PATIENTS AND METHODS: YY1 and NEAT1 expressions in anterior lens capsule collected from diabetic cataract (DC) patients and normal controls were examined by quantitative real-time polymerase chain reaction (qRT-PCR) analysis, and their correlation was analyzed. The binding site between YY1 and NEAT1 sequences was predicted by JASPAR and detected by Dual-Luciferase reporter assay and chromatin immunoprecipitation (ChIP) assay. The proliferation and apoptosis of high-glucose-induced cells with NEAT1 knockdown were detected. Potential downstream targets of NEAT1 were predicted by bioinformatics and detected by Dual-Luciferase reporter assay. RESULTS: YY1 and NEAT1 expressions in the anterior capsule tissue of DC lens were remarkably reduced and positively correlated. Dual-Luciferase reporter assay and ChIP confirmed that YY1 could bind to locus 2 of NEAT1. Knockdown of NEAT1 inhibited proliferation while promoted apoptosis under high glucose conditions. Further mechanism studies revealed that knockdown of NEAT1 could upregulate microRNA-205-3p, and MMP16 was a potential target of miR-205. CONCLUSIONS: The low expression of YY1 induces NEAT1 downregulation, which regulates microRNA-205-3p/MMP16 axis and thus participates in the development of DC.
机译:目的:我们旨在调查Neat1在糖尿病白内障发病机制中的可能作用和机制。患者和方法:通过定量实时聚合酶链反应(QRT-PCR)分析检查从糖尿病白内障(DC)患者的前镜囊中的YY1和Neat1表达,并分析了它们的相关性。通过JASPAR预测YY1和NEAT1序列之间的结合位点,并通过双荧光素酶报告酶测定和染色质免疫沉淀(芯片)测定检测。检测高葡萄糖诱导细胞的增殖和凋亡。通过生物信息学预测整体1的潜在下游靶位,并通过双荧光素酶报告结果检测。结果:DC透镜的前囊组织中的YY1和Neat1表达显着降低和正相关。双荧光素酶报告器测定和芯片证实,YY1可以与Neat1的基因座2结合。 Neat1的敲低抑制增殖,同时在高葡萄糖条件下促进细胞凋亡。进一步的机制研究表明,Neat1的敲低可以上调MicroRNA-205-3P,MMP16是miR-205的潜在靶标。结论:YY1的低表达诱导整套下调,该下调调节MicroRNA-205-3P / MMP16轴,从而参与DC的开发。

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