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长链非编码RNA FENDRR作为原发性高血压的潜在标志物，并通过miR-423-5p/Nox4轴调节人脐静脉内皮细胞功能障碍。

LncRNA FENDRR Servers as a Possible Marker of Essential Hypertension and Regulates Human Umbilical Vein Endothelial Cells Dysfunction via miR-423-5p/Nox4 Axis.

作者信息

Zhao Xiaojian, Wang Chen, Liu Min, Meng Fansen, Liu Kai

机构信息

Department of Hypertension, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, People's Republic of China.

Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People's Republic of China.

出版信息

Int J Gen Med. 2022 Mar 5;15:2529-2540. doi: 10.2147/IJGM.S338147. eCollection 2022.

DOI:10.2147/IJGM.S338147
PMID:35282648
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8906997/
Abstract

PURPOSE

Essential hypertension (EH) is an intricate non-communicable infirmity and lncRNAs are validated as essential mediators in EH. The study aimed to propose the expression pattern of FENDRR and miR-423-5p, substantiate the potential mechanism of FENDRR/miR-423-5p/Nox4 axis in EH.

PATIENTS AND METHODS

The expression of FENDRR and miR-423-5p was evaluated by qRT-PCR and the clinical significance was explored by the ROC curve. Pearson correlation indicated the relationship between FENDRR and miR-423-5p. The function of FENDRR and miR-423-5p on HUVECs was clarified by CCK-8 assay, Transwell assay, and flow cytometry. Western blot was used to assess the relative protein expression of Nox4.

RESULTS

FENDRR was highly expressed and miR-423-5p was lowly expressed in EH patients and a negative correlation between them was determined. FENDRR might serve as a predictive diagnosis in differentiating EH patients. Knockdown of FENDRR or overexpression of miR-423-5p showed expansionary effects in cell proliferation, cell migration, and inhibiting cell apoptosis. Meanwhile, miR-423-5p was determined as a target of FENDRR and mediated the function of FENDRR on HUVECs. Moreover, Nox4 is a down-streaming target gene of miR-423-5p. The protein expression of Nox4 was regulated by the alternation of miR-423-5p expression.

CONCLUSION

FENDRR played an energetic role in EH and contributed to HUVECs dysfunction by restricting cell proliferation, suppressing cell migration, and accelerating cell apoptosis by manipulating the miR-423-5p/Nox4 axis.

摘要

目的

原发性高血压（EH）是一种复杂的非传染性疾病，长链非编码RNA（lncRNAs）被证实是EH的重要介质。本研究旨在提出FENDRR和miR-423-5p的表达模式，证实FENDRR/miR-423-5p/Nox4轴在EH中的潜在机制。

患者和方法

采用qRT-PCR评估FENDRR和miR-423-5p的表达，并通过ROC曲线探讨其临床意义。Pearson相关性分析表明FENDRR与miR-423-5p之间的关系。通过CCK-8法、Transwell法和流式细胞术阐明FENDRR和miR-423-5p对人脐静脉内皮细胞（HUVECs）的作用。采用蛋白质免疫印迹法评估Nox4的相对蛋白表达。

结果

EH患者中FENDRR高表达，miR-423-5p低表达，且二者呈负相关。FENDRR可作为鉴别EH患者的预测诊断指标。敲低FENDRR或过表达miR-423-5p对细胞增殖、细胞迁移具有促进作用，并抑制细胞凋亡。同时，miR-423-5p被确定为FENDRR的靶标，并介导FENDRR对HUVECs的作用。此外，Nox4是miR-423-5p的下游靶基因。miR-423-5p表达的改变可调节Nox4的蛋白表达。

结论

FENDRR在EH中发挥重要作用，通过调控miR-423-5p/Nox4轴限制细胞增殖、抑制细胞迁移并加速细胞凋亡，导致HUVECs功能障碍。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cffa/8906997/1c0b55cad1bb/IJGM-15-2529-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cffa/8906997/477cf3fa38e0/IJGM-15-2529-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cffa/8906997/58d72d324d3a/IJGM-15-2529-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cffa/8906997/92e242a23dff/IJGM-15-2529-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cffa/8906997/2ef9dff90975/IJGM-15-2529-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cffa/8906997/d531e610c100/IJGM-15-2529-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cffa/8906997/1c0b55cad1bb/IJGM-15-2529-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cffa/8906997/477cf3fa38e0/IJGM-15-2529-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cffa/8906997/58d72d324d3a/IJGM-15-2529-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cffa/8906997/92e242a23dff/IJGM-15-2529-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cffa/8906997/2ef9dff90975/IJGM-15-2529-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cffa/8906997/d531e610c100/IJGM-15-2529-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cffa/8906997/1c0b55cad1bb/IJGM-15-2529-g0006.jpg

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