LncRNA AC100865.1 regulates macrophage adhesion and ox-LDL intake through miR-7/GDF5 pathway

IF 4.4 2区生物学 Q2 CELL BIOLOGY

Cellular signalling Pub Date : 2025-03-15 DOI:10.1016/j.cellsig.2025.111748

Yong Ren , Jiarong Liang , Baofeng Chen , Xiangyang Liu , Jinfeng Chen , Xiangying Liu , Yunxian Chen

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引用次数: 0

Abstract

Objectives

Cardiovascular disease (CVD) accounts for over 40 % of deaths related to diseases among residents. Atherosclerosis (AS) and its associated thrombosis are the primary causes of CVD. LncRNA AC100865.1, a newly identified lncRNA, has shown potential as a diagnostic biomarker for AS. This study aims to evaluate the therapeutic value of lncRNA AC100865.1 in AS.

Methods

Real-time PCR was conducted to assess the relative expression of lncRNA AC100865.1 in Peripheral Blood Mononuclear Cell (PBMC) samples from 50 CVD patients and 50 healthy controls. lncRNA AC100865.1 was overexpressed in RAW264.7 cells to measure its effects on adhesion and oxidized low-density lipoprotein (ox-LDL) uptake. Flow cytometry was utilized to identify the pathway mediating these processes. The luciferase assay and knockout rescue experiments were performed to elucidate the downstream signaling pathways involved.

Results

lncRNA AC100865.1 expression was found to be downregulated in CVD patients. Overexpression of lncRNA AC100865.1 significantly enhanced the adhesion capacity of RAW264.7 cells. Luciferase reporter assays and flow cytometry indicated that this effect is mediated through the miR-7/GDF5/p38/LFA-1 pathway. Furthermore, lncRNA AC100865.1 notably increased ox-LDL uptake by macrophages via upregulation of CD36 expression.

Conclusion

Overexpression of lncRNA AC100865.1 enhances the adhesion of RAW264.7 cells through the miR-7/GDF5/p38/LFA-1 pathway and increases ox-LDL uptake by elevating CD36 levels. These findings suggest that circulating lncRNA AC100865.1 may serve not only as an early diagnostic marker for CVD but also as a potential therapeutic target, offering new prospects for CVD treatment.

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LncRNA AC100865.1通过miR-7/GDF5途径调控巨噬细胞粘附和ox-LDL摄入。

目的：心血管疾病（CVD）占居民疾病相关死亡的40% %以上。动脉粥样硬化（AS）及其相关血栓形成是心血管疾病的主要原因。LncRNA AC100865.1是一种新发现的LncRNA，已显示出作为as诊断生物标志物的潜力。本研究旨在评价lncRNA AC100865.1在AS中的治疗价值。方法：采用Real-time PCR检测50例CVD患者和50例健康对照者外周血单核细胞（PBMC）中lncRNA AC100865.1的相对表达量。lncRNA AC100865.1在RAW264.7细胞中过表达，以测量其对粘附和氧化低密度脂蛋白（ox-LDL）摄取的影响。流式细胞术被用来鉴定介导这些过程的途径。荧光素酶检测和基因敲除修复实验阐明了下游信号通路。结果：在CVD患者中发现lncRNA AC100865.1表达下调。过表达lncRNA AC100865.1显著增强RAW264.7细胞的粘附能力。荧光素酶报告基因检测和流式细胞术表明，这种作用是通过miR-7/GDF5/p38/LFA-1途径介导的。此外，lncRNA AC100865.1通过上调CD36表达显著增加巨噬细胞对ox-LDL的摄取。结论：过表达lncRNA AC100865.1通过miR-7/GDF5/p38/LFA-1途径增强RAW264.7细胞的粘附，并通过升高CD36水平增加ox-LDL的摄取。这些发现提示，循环lncRNA AC100865.1不仅可以作为CVD的早期诊断标志物，还可以作为潜在的治疗靶点，为CVD的治疗提供新的前景。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cellular signalling 生物-细胞生物学

CiteScore

8.40

自引率

0.00%

发文量

250

审稿时长

27 days

期刊介绍： Cellular Signalling publishes original research describing fundamental and clinical findings on the mechanisms, actions and structural components of cellular signalling systems in vitro and in vivo. Cellular Signalling aims at full length research papers defining signalling systems ranging from microorganisms to cells, tissues and higher organisms.