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长链非编码 RNA GAS5 通过 microRNA-194-3p/TXNIP 轴加重冠状动脉粥样硬化。

Long Non-coding RNA GAS5 Worsens Coronary Atherosclerosis Through MicroRNA-194-3p/TXNIP Axis.

机构信息

Department of Cardiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100043, China.

Department of Cardiology, Beijing Tsinghua Changgung Hospital, Tsinghua University, No. 168 Litang Road, Changping District, Beijing, 102218, China.

出版信息

Mol Neurobiol. 2021 Jul;58(7):3198-3207. doi: 10.1007/s12035-021-02332-x. Epub 2021 Feb 27.

Abstract

It is formerly conducted that long non-coding RNA growth arrest-specific 5 (GAS5) is involved in the process of coronary atherosclerosis (AS). The regulatory effects of GAS5 on the microRNA (miR)-194-3p/thioredoxin-interacting protein (TXNIP) axis in AS have been insufficiently explored yet. Thereafter, this work is started from GAS5/miR-194-3p/TXNIP axis in AS. AS rats were modeled to obtain their coronary vascular tissues and endothelial cells (ECs), in which GAS5, miR-194-3p, and TXNIP expression were tested. ECs were identified by immunohistochemistry. The mechanism among GAS5, miR-194-3p, and TXNIP was determined. ECs were transfected with inhibited GAS5 or overexpressed miR-194-3p to decipher their functions in proliferation and apoptosis of ECs in AS. Raised GAS5 and TXNIP and degraded miR-194-3p expression levels exhibited in AS. GAS5 bound to miR-194-3p while miR-194-3p targeted TXNIP. Depleting GAS5 or restoring miR-194-3p enhanced proliferation and depressed apoptosis of ECs in AS. This work clearly manifests that inhibited GAS5 facilitates the growth of ECs through miR-194-3p-targeted TXNIP in AS, consolidating the basal reference to the curing for AS.

摘要

先前的研究表明,长链非编码 RNA 生长停滞特异性基因 5(GAS5)参与了冠状动脉粥样硬化(AS)的发生过程。然而,GAS5 对 AS 中 microRNA(miR)-194-3p/硫氧还蛋白相互作用蛋白(TXNIP)轴的调节作用尚未得到充分探索。因此,本研究从 AS 中的 GAS5/miR-194-3p/TXNIP 轴入手。构建 AS 大鼠模型,获取其冠状动脉血管组织和内皮细胞(EC),检测 GAS5、miR-194-3p 和 TXNIP 的表达。通过免疫组织化学鉴定 EC。确定 GAS5、miR-194-3p 和 TXNIP 之间的机制。用抑制 GAS5 或过表达 miR-194-3p 转染 EC,以阐明它们在 AS 中 EC 增殖和凋亡中的作用。AS 中 GAS5 和 TXNIP 升高,miR-194-3p 降解。GAS5 与 miR-194-3p 结合,而 miR-194-3p 靶向 TXNIP。敲低 GAS5 或恢复 miR-194-3p 可促进 AS 中 EC 的增殖并抑制其凋亡。本研究清楚地表明,在 AS 中,抑制 GAS5 通过 miR-194-3p 靶向 TXNIP 促进 EC 的生长,为 AS 的治疗提供了基础参考。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3da/8257541/de6de6d89a5c/12035_2021_2332_Fig1_HTML.jpg

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