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长链非编码 RNA PCA3 通过负调控 miR-124-3p/ITGB1 轴抑制颈动脉狭窄和血管平滑肌细胞功能。

lncRNA PCA3 Suppressed Carotid Artery Stenosis and Vascular Smooth Muscle Cell Function via Negatively Modulating the miR-124-3p/ITGB1 Axis.

机构信息

The Affiliated Taizhou Second People's Hospital of Yangzhou University, Taizhou, China.

Department of Neurology, Huai'an Hospital Affiliated to Xuzhou Medical University, Huai'an, China.

出版信息

Clin Appl Thromb Hemost. 2023 Jan-Dec;29:10760296231190383. doi: 10.1177/10760296231190383.

DOI:10.1177/10760296231190383
PMID:37583257
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10467385/
Abstract

BACKGROUND & OBJECTIVES: Due to the hidden pathogen, carotid artery stenosis (CAS) always occurred at an advanced stage leading to serious sequelae and even deaths. The significance of long noncoding RNA (lncRNA) prostate cancer antigen 3 (PCA3) in CAS incidence and progression were evaluated aiming to explore a potential target for its therapy.

MATERIALS AND METHODS

Serum samples were collected from 83 asymptomatic CAS patients and 52 healthy individuals and PCA3 was compared using polymerase chain reaction (PCR). The PCA3 levels were compared between stable and unstable plaque in CAS patients. The effect of PCA3 on vascular smooth muscle cells (VSMCs) proliferation and motility was assessed by CCK8 and transwell assay.

RESULTS

PCA3 was downregulated in CAS patients and their unstable plaque tissues compared with healthy individuals and stable plaque, respectively. Reduced PCA3 could discriminate CAS patients with relatively high sensitivity and specificity and were associated with higher total cholesterol level and stenosis degree, unstable plaque, and complications. PCA3 downregulation predicted the adverse outcomes of CAS patients. In VSMCs, overexpressing PCA3 significantly suppressed cell proliferation, migration, and invasion, which was alleviated by miR-124-3p/ITGB1 axis.

CONCLUSION

PCA3 served as a biomarker of CAS and regulates the function of VSMCs through sponging miR-124-3p/ITGB1 and indirectly influence the stability of plaque.

摘要

背景与目的

由于隐匿性病因,颈动脉狭窄(CAS)常在疾病进展到晚期才被发现,导致严重的后遗症甚至死亡。本研究旨在评估长链非编码 RNA(lncRNA)前列腺癌抗原 3(PCA3)在 CAS 发病和进展中的意义,以期探索其治疗的潜在靶点。

材料与方法

收集 83 例无症状性 CAS 患者和 52 例健康个体的血清样本,采用聚合酶链反应(PCR)比较 PCA3。比较 CAS 患者稳定斑块和不稳定斑块之间的 PCA3 水平。通过 CCK8 和 Transwell 测定评估 PCA3 对血管平滑肌细胞(VSMCs)增殖和迁移的影响。

结果

与健康个体和稳定斑块相比,CAS 患者及其不稳定斑块组织中 PCA3 表达下调。降低的 PCA3 可区分 CAS 患者,具有较高的灵敏度和特异性,且与总胆固醇水平升高、狭窄程度、不稳定斑块和并发症相关。PCA3 下调预测了 CAS 患者的不良结局。在 VSMCs 中,过表达 PCA3 显著抑制细胞增殖、迁移和侵袭,而 miR-124-3p/ITGB1 轴可减轻这种抑制作用。

结论

PCA3 可作为 CAS 的生物标志物,通过海绵吸附 miR-124-3p/ITGB1 调节 VSMCs 的功能,间接影响斑块的稳定性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57d4/10467385/f9edb3511e0a/10.1177_10760296231190383-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57d4/10467385/c8059febd640/10.1177_10760296231190383-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57d4/10467385/01917f383785/10.1177_10760296231190383-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57d4/10467385/cd8d4f233fc7/10.1177_10760296231190383-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57d4/10467385/f9edb3511e0a/10.1177_10760296231190383-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57d4/10467385/c8059febd640/10.1177_10760296231190383-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57d4/10467385/01917f383785/10.1177_10760296231190383-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57d4/10467385/cd8d4f233fc7/10.1177_10760296231190383-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57d4/10467385/f9edb3511e0a/10.1177_10760296231190383-fig4.jpg

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