LncRNA XIST promotes neovascularization in diabetic retinopathy by regulating miR-101-3p/VEGFA.

IF 1.6 4区 医学 Q4 ENDOCRINOLOGY & METABOLISM
Weina Fu, Yunyan Ye, Feng Hu
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Abstract

Objective: This study sought to investigate the regulation of long noncoding RNA (lncRNA) XIST on the microRNA (miR)-101-3p/vascular endothelial growth factor A (VEGFA) axis in neovascularization in diabetic retinopathy (DR).

Materials and methods: Serum of patients with DR was extracted for the analysis of XIST, miR-101-3p, and VEGFA expression levels. High glucose (HG)-insulted HRMECs and DR model rats were treated with lentiviral vectors. MTT, transwell, and tube formation assays were performed to evaluate cell viability, migration, and angiogenesis, and ELISA was conducted to detect the levels of inflammatory cytokines. Dual-luciferase reporter, RIP, and RNA pull-down experiments were used to validate the relationships among XIST, miR-101-3p, and VEGFA.

Results: XIST and VEGFA were upregulated and miR-101-3p was downregulated in serum from patients with DR. XIST knockdown inhibited proliferation, migration, vessel tube formation, and inflammatory responsein HG-treated HRMECs, whereas the above effects were nullified by miR-101-3p inhibition or VEGFA overexpression. miR-101-3p could bind to XIST and VEGFA. XIST promoted DR development in rats by regulating the miR-101-3p/VEGFA axis.

Conclusion: LncRNA XIST promotes VEGFA expression by downregulating miR-101-3p, thereby stimulating angiogenesis and inflammatory response in DR.

LncRNA XIST通过调节miR-101-3p/VEGFA促进糖尿病视网膜病变中的新生血管形成。
研究目的本研究旨在探讨长非编码 RNA(lncRNA)XIST 在糖尿病视网膜病变(DR)新生血管形成过程中对 microRNA(miR)-101-3p/血管内皮生长因子 A(VEGFA)轴的调控作用:提取 DR 患者的血清以分析 XIST、miR-101-3p 和 VEGFA 的表达水平。用慢病毒载体处理高糖(HG)诱导的 HRMECs 和 DR 模型大鼠。进行 MTT、transwell 和管形成试验以评估细胞活力、迁移和血管生成,并用 ELISA 检测炎症细胞因子的水平。使用双荧光素酶报告、RIP 和 RNA 拉取实验来验证 XIST、miR-101-3p 和 VEGFA 之间的关系:结果:在DR患者的血清中,XIST和VEGFA上调,miR-101-3p下调。敲除 XIST 可抑制 HG 处理的 HRMECs 的增殖、迁移、血管管形成和炎症反应,而抑制 miR-101-3p 或过表达 VEGFA 则会使上述效应无效。XIST通过调节miR-101-3p/VEGFA轴促进了大鼠DR的发生:结论:LncRNA XIST 通过下调 miR-101-3p 促进 VEGFA 的表达,从而刺激 DR 的血管生成和炎症反应。
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来源期刊
Archives of Endocrinology Metabolism
Archives of Endocrinology Metabolism Medicine-Endocrinology, Diabetes and Metabolism
CiteScore
2.90
自引率
5.90%
发文量
107
审稿时长
7 weeks
期刊介绍: The Archives of Endocrinology and Metabolism - AE&M – is the official journal of the Brazilian Society of Endocrinology and Metabolism - SBEM, which is affiliated with the Brazilian Medical Association. Edited since 1951, the AE&M aims at publishing articles on scientific themes in the basic translational and clinical area of Endocrinology and Metabolism. The printed version AE&M is published in 6 issues/year. The full electronic issue is open access in the SciELO - Scientific Electronic Library Online e at the AE&M site: www.aem-sbem.com. From volume 59 on, the name was changed to Archives of Endocrinology and Metabolism, and it became mandatory for manuscripts to be submitted in English for the online issue. However, for the printed issue it is still optional for the articles to be sent in English or Portuguese. The journal is published six times a year, with one issue every two months.
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