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长链非编码RNA HIF1A-AS1在颅内动脉瘤中上调,并通过上调TGF-β1参与血管平滑肌细胞增殖的调控。

Long non-coding RNA HIF1A-AS1 is upregulated in intracranial aneurysms and participates in the regulation of proliferation of vascular smooth muscle cells by upregulating TGF-β1.

作者信息

Xu Jiaming, Zhang Yang, Chu Lisheng, Chen Weiyan, Du Yueguang, Gu Jingjing

机构信息

Department of Neurosurgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310000, P.R. China.

Department of Pathology and Pathophysiology, School of Basic Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310009, P.R. China.

出版信息

Exp Ther Med. 2019 Mar;17(3):1797-1801. doi: 10.3892/etm.2018.7144. Epub 2018 Dec 28.

Abstract

Long non-coding (lnc)RNA hypoxia inducible factor 1α-antisense RNA 1 (HIF1A-AS1) not only participates in different types of malignancies, but also serves pivotal roles in thoracic aortic aneurysms, which suggests its possible involvement in intracranial aneurysms. Therefore, the present study aimed to investigate its involvement in intracranial aneurysms. Expression levels of HIF1A-AS1 and transforming growth factor (TGF)-β1 in the blood of patients with intracranial aneurysms and healthy controls were detected using reverse transcription-quantitative polymerase chain reaction. The diagnostic value of blood HIF1A-AS1 for intracranial aneurysms was analyzed using receiver operating characteristic curve analysis. A HIF1A-AS1 expression vector was constructed and transfected into human vascular smooth muscle cells (VSMCs) and the effects on cell proliferation and TGF-β1 expression were explored using the Cell Counting kit-8 assay and western blot analysis, respectively. Upregulated HIF1A-AS1 expression levels in blood were observed in patients with intracranial aneurysms when compared with controls. Notably, upregulated HIF1A-AS1 expression effectively distinguished patients with intracranial aneurysms from healthy controls. Furthermore, HIF1A-AS1 and TGF-β1 expression levels were positively correlated with intracranial aneurysms. HIF1A-AS1 overexpression also upregulated TGF-β1 expression and inhibited VSMC proliferation. Although TGF-β1 treatment had no significant effect on HIF1A-AS1 expression, TGF-β inhibitor significantly reduced the effects of HIF1A-AS1 overexpression on cell proliferation. It was therefore concluded that HIF1A-AS1 may participate in intracranial aneurysms by regulating VSMC proliferation through the upregulation of TGF-β1.

摘要

长链非编码(lnc)RNA缺氧诱导因子1α反义RNA 1(HIF1A-AS1)不仅参与不同类型的恶性肿瘤,还在胸主动脉瘤中起关键作用,这表明其可能与颅内动脉瘤有关。因此,本研究旨在探讨其在颅内动脉瘤中的作用。采用逆转录-定量聚合酶链反应检测颅内动脉瘤患者和健康对照者血液中HIF1A-AS1和转化生长因子(TGF)-β1的表达水平。使用受试者工作特征曲线分析来分析血液中HIF1A-AS1对颅内动脉瘤的诊断价值。构建HIF1A-AS1表达载体并将其转染到人血管平滑肌细胞(VSMC)中,分别使用细胞计数试剂盒-8法和蛋白质印迹分析来探讨其对细胞增殖和TGF-β1表达的影响。与对照组相比,颅内动脉瘤患者血液中HIF1A-AS1表达水平上调。值得注意的是,上调的HIF1A-AS1表达能有效区分颅内动脉瘤患者和健康对照者。此外,HIF1A-AS1和TGF-β1表达水平与颅内动脉瘤呈正相关。HIF1A-AS1过表达还上调了TGF-β1表达并抑制了VSMC增殖。虽然TGF-β1处理对HIF1A-AS1表达没有显著影响,但TGF-β抑制剂显著降低了HIF1A-AS1过表达对细胞增殖的影响。因此得出结论,HIF1A-AS1可能通过上调TGF-β1来调节VSMC增殖,从而参与颅内动脉瘤的发生。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/caa2/6395997/1fbfcc05c3c5/etm-17-03-1797-g00.jpg

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