环状 RNA circ_0002984 通过 Let-7a-5p/KLF5 通路促进氧化-LDL 诱导的血管平滑肌细胞的增殖和迁移

IF 3.4 3区 医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS
Cardiovascular Toxicology Pub Date : 2024-11-01 Epub Date: 2024-08-24 DOI:10.1007/s12012-024-09911-z
Feng Chen, Ruilai Jiang, Xiufeng Yu
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引用次数: 0

摘要

环状 RNA(circRNA)在动脉粥样硬化(AS)的进展过程中发挥着重要作用。本研究旨在探索 circ_0002984 在氧化低密度脂蛋白(ox-LDL)介导的人血管平滑肌细胞(HVSMCs)中的确切作用和机制。通过用氧化-LDL处理人血管平滑肌细胞,构建了平滑肌细胞表型转换模型。通过实时定量 PCR 或 Western 印迹检测了 circ_0002984、let-7a-5p 和 kruppel-like factor 5 (KLF5) 的水平。细胞计数试剂盒-8(CCK-8)、EdU 染色、伤口愈合试验、透孔试验和流式细胞术检测了细胞的增殖、迁移和凋亡。通过 Western 印迹检测了裂解的天冬酶-3 和 KLF5 的表达。通过双荧光素酶报告实验或 RIP 实验验证了 let-7a-5p 与 circ_0002984 或 KLF5 之间的关系。结果显示,在AS患者和氧化-LDL处置的HVSMC中,circ_0002984和KLF5上调,而let-7a-5p下调。沉默circ_0002984可抑制氧化-LDL刺激的HVSMC的增殖和迁移,并促进其凋亡。此外,circ_0002984还能通过let-7a-5p调节ox-LDL导致的HVSMCs的增殖、迁移和凋亡。此外,KLF5是let-7a-5p的靶标,其过表达可逆转let-7a-5p对ox-LDL处理的HVSMC增殖、迁移和凋亡的影响。此外,circ_0002984还能通过吸收let-7a-5p正向调节KLF5的表达。KLF5沉默可逆转circ_0002984对经ox-LDL处理的HVSMC增殖和迁移的促进作用。综上所述,消耗circ_0002984可抑制ox-LDL刺激的HVSMC的增殖和迁移,这可能是通过调节let-7a-5p/KLF5轴实现的。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Circular RNA circ_0002984 Facilitates the Proliferation and Migration of Ox-LDL-Induced Vascular Smooth Muscle Cells via the Let-7a-5p/KLF5 Pathway.

Circular RNA circ_0002984 Facilitates the Proliferation and Migration of Ox-LDL-Induced Vascular Smooth Muscle Cells via the Let-7a-5p/KLF5 Pathway.

Circular RNAs (circRNAs) play an important role in the progression of atherosclerosis (AS). This study aimed to explore the exact role and mechanism of circ_0002984 in oxidized low-density lipoprotein (ox-LDL)-mediated human vascular smooth muscle cells (HVSMCs). The model of smooth muscle cell phenotype switching was constructed by treating HVSMCs with ox-LDL. The levels of circ_0002984, let-7a-5p, and kruppel-like factor 5 (KLF5) were measured by quantitative real-time PCR or western blot assay. Cell proliferation, migration, and apoptosis were detected by Cell Counting Kit-8 (CCK-8), EdU staining, wound healing assay, transwell assay, and flow cytometry. The expression of cleaved-caspase-3 and KLF5 was examined by western blot. The relationship between let-7a-5p and circ_0002984 or KLF5 was verified by dual-luciferase reporter assay or RIP assay. The results showed that circ_0002984 and KLF5 were up-regulated, while let-7a-5p was down-regulated in AS patients and ox-LDL-disposed HVSMCs. Silence of circ_0002984 suppressed proliferation and migration, and promoted apoptosis in ox-LDL-stimulated HVSMCs. Moreover, circ_0002984 sponged let-7a-5p to regulate the proliferation, migration, and apoptosis in ox-LDL-resulted HVSMCs. In addition, KLF5 was a target of let-7a-5p and its overexpression reversed the effect of let-7a-5p on the proliferation, migration, and apoptosis in ox-LDL-treated HVSMCs. Also, circ_0002984 positively regulated KLF5 expression by absorbing let-7a-5p. The promotion effect of circ_0002984 on the proliferation and migration of ox-LDL-treated HVSMCs was reversed by KLF5 silencing. Taken together, depletion of circ_0002984 inhibited the proliferation and migration of ox-LDL-stimulated HVSMCs, which might be achieved by modulating the let-7a-5p/KLF5 axis.

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来源期刊
Cardiovascular Toxicology
Cardiovascular Toxicology 医学-毒理学
CiteScore
6.60
自引率
3.10%
发文量
61
审稿时长
>12 weeks
期刊介绍: Cardiovascular Toxicology is the only journal dedicated to publishing contemporary issues, timely reviews, and experimental and clinical data on toxicological aspects of cardiovascular disease. CT publishes papers that will elucidate the effects, molecular mechanisms, and signaling pathways of environmental toxicants on the cardiovascular system. Also covered are the detrimental effects of new cardiovascular drugs, and cardiovascular effects of non-cardiovascular drugs, anti-cancer chemotherapy, and gene therapy. In addition, Cardiovascular Toxicology reports safety and toxicological data on new cardiovascular and non-cardiovascular drugs.
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