长链非编码 RNA HCG18 通过调节血管平滑肌细胞的增殖和凋亡，通过 miR-103a-3p/HMGA2 轴影响主动脉夹层。

LncRNA HCG18 affects aortic dissection through the miR-103a-3p/HMGA2 axis by modulating proliferation and apoptosis of vascular smoothing muscle cells.

机构信息

Department of Invasive Technology, Ningde Municipal Hospital of Ningde Normal University, Ningde City, Fujian Province, China.

出版信息

Clinics (Sao Paulo). 2024 Jul 31;79:100400. doi: 10.1016/j.clinsp.2024.100400. eCollection 2024.

DOI:10.1016/j.clinsp.2024.100400

PMID:39089097

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11342200/

Abstract

BACKGROUND

Aortic Dissection (AD) is a vascular disease with a high mortality rate and limited treatment strategies. The current research analyzed the function and regulatory mechanism of lncRNA HCG18 in AD.

METHODS

HCG18, miR-103a-3p, and HMGA2 levels in the aortic tissue of AD patients were examined by RT-qPCR. After transfection with relevant plasmids, the proliferation of rat aortic Vascular Smoothing Muscle Cells (VSMCs) was detected by CCK-8 and colony formation assay, Bcl-2 and Bax was measured by Western blot, and apoptosis was checked by flow cytometry. Then, the targeting relationship between miR-103a-3p and HCG18 or HMGA2 was verified by bioinformation website analysis and dual luciferase reporter assay. Finally, the effect of HCG18 was verified in an AD rat model induced by β-aminopropionitrile.

RESULTS

HCG18 and HMGA2 were upregulated and miR-103a-3p was downregulated in the aortic tissues of AD patients. Downregulating HCG18 or upregulating miR-103a-3p enhanced the proliferation of VSMCs and limited cell apoptosis. HCG18 promoted HMGA2 expression by competing with miR-103a-3p and restoring HMGA2 could impair the effect of HCG18 downregulation or miR-103a-3p upregulation in mediating the proliferation and apoptosis of VSMCs. In addition, down-regulation of HCG18 could improve the pathological injury of the aorta in AD rats.

CONCLUSION

HCG18 reduces proliferation and induces apoptosis of VSMCs through the miR-103a-3p/HMGA2 axis, thus aggravating AD.

摘要

背景

主动脉夹层（AD）是一种死亡率高、治疗策略有限的血管疾病。本研究分析了长链非编码 RNA HCG18 在 AD 中的功能和调控机制。

方法

通过 RT-qPCR 检测 AD 患者主动脉组织中 HCG18、miR-103a-3p 和 HMGA2 的水平。转染相关质粒后，通过 CCK-8 和集落形成实验检测大鼠主动脉血管平滑肌细胞（VSMCs）的增殖，通过 Western blot 检测 Bcl-2 和 Bax 的表达，通过流式细胞术检测细胞凋亡。然后，通过生物信息网站分析和双荧光素酶报告基因实验验证 miR-103a-3p 与 HCG18 或 HMGA2 的靶向关系。最后，在β-氨基丙腈诱导的 AD 大鼠模型中验证 HCG18 的作用。

结果

AD 患者主动脉组织中 HCG18 和 HMGA2 上调，miR-103a-3p 下调。下调 HCG18 或上调 miR-103a-3p 可增强 VSMCs 的增殖并限制细胞凋亡。HCG18 通过与 miR-103a-3p 竞争促进 HMGA2 表达，并恢复 HMGA2 可削弱 HCG18 下调或 miR-103a-3p 上调在介导 VSMCs 增殖和凋亡中的作用。此外，下调 HCG18 可改善 AD 大鼠主动脉的病理损伤。