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lncNALT 敲低通过 PTEN/PI3K/AKT 通路改善高血压性视网膜病变。

lncNALT knockdown ameliorates hypertensive retinopathy via PTEN/PI3K/AKT pathway.

机构信息

Department of Ophthalmology, Suining Central Hospital, Suining, Sichuan, China.

Department of Cardiovascular, Suining Central Hospital, Suining, Sichuan, China.

出版信息

Bioengineered. 2022 Jul-Dec;13(7-12):15003-15012. doi: 10.1080/21655979.2023.2180591.

Abstract

This study aimed to explore the role of the long non-coding RNA NOTCH1-associated lncRNA in T cell acute lymphoblastic leukemia (lncNALT) in the pathogenesis of hypertensive retinopathy (HR). LncNALT expression levels were determined using reverse transcription-quantitative polymerase chain reaction. The effects of lncNALT knockdown on the viability, proliferation, migration, and invasion of human retinal microvascular endothelial cells (RMECs) were determined via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide, 5-ethynyl-2'-deoxyuridine staining, and Transwell assays. Protein expression levels were determined using western blotting. We found that lncNALT expression levels were increased in RMECs treated with hydrogen peroxide (HO), while the knockdown of lncNALT rescued the viability, proliferation, migration, and invasion of RMECs treated with HO. Moreover, lncNALT interacted with ELAV like RNA binding protein 1 to affect the phosphatase and tensin homolog (PTEN) expression. Knockdown of lncNALT enhanced the viability, proliferation, migration, and invasion of RMECs via the PTEN/phosphoinositide 3-kinase (PI3K)/serine-threonine kinase (AKT) pathway. Taken together, knockdown of lncNALT enhanced the viability, proliferation, migration, and invasion of RMECs via the PTEN/PI3K/AKT pathway, suggesting that lncNALT could be a potential therapeutic target for patients with HR.

摘要

本研究旨在探讨长链非编码 RNA NOTCH1 相关 lncRNA 在 T 细胞急性淋巴细胞白血病(lncNALT)发病机制中在高血压性视网膜病变(HR)中的作用。采用逆转录定量聚合酶链反应测定 lncNALT 表达水平。通过 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐、5-乙炔基-2'-脱氧尿苷染色和 Transwell 分析测定 lncNALT 敲低对人视网膜微血管内皮细胞(RMEC)活力、增殖、迁移和侵袭的影响。采用蛋白质印迹法测定蛋白表达水平。我们发现,过氧化氢(HO)处理的 RMEC 中 lncNALT 表达水平升高,而 lncNALT 的敲低挽救了 HO 处理的 RMEC 的活力、增殖、迁移和侵袭。此外,lncNALT 与 RNA 结合蛋白 1 相互作用,影响磷酸酶和张力蛋白同源物(PTEN)的表达。lncNALT 的敲低通过 PTEN/磷酸肌醇 3-激酶(PI3K)/丝氨酸苏氨酸激酶(AKT)通路增强了 RMEC 的活力、增殖、迁移和侵袭。总之,lncNALT 的敲低通过 PTEN/PI3K/AKT 通路增强了 RMEC 的活力、增殖、迁移和侵袭,表明 lncNALT 可能是 HR 患者的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce33/10234215/0827d3c56b25/KBIE_A_2180591_UF0001_OC.jpg

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