Gu Mingming, Liu Kun, Xiong Hui, You Qingsheng
Department of Cardiothoracic Surgery, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu Province, China.
Heliyon. 2024 Jan 17;10(2):e24541. doi: 10.1016/j.heliyon.2024.e24541. eCollection 2024 Jan 30.
MicroRNA-130a-3p (miR-130a-3p) has been reported as closely related to atherosclerosis (AS). This study is to survey the effects of miR-130a-3p in endothelial cells (ECs) treated with oxidized low-density lipoprotein (ox-LDL) and explore underlying mechanisms. The proliferation and apoptosis of ox-LDL-treated HUVEC cells were determined by CCK-8, EdU, and flow cytometry assays. ELISA and Western blot analysis measured the expressions of cytokines and protein levels. Bioinformatics and dual-luciferase reporter assay were performed to predict and confirm that Mitogen-activated protein kinase 8 (MAPK8) was a direct target of miR-130a-3p, and MAPK8 was negatively associated with miR-130a-3p. As expected, miR-130a-3p was down-regulated in ox-LDL-treated HUVEC cells, and up-regulation of miR-130a-3p promoted proliferation and inhibited apoptosis of ox-LDL-treated HUVEC cells. Furthermore, miR-130a-3p mimics suppressed the expressions of TNF-α and IL-6 and decreased the protein levels of VCAM-1, ICAM-1 and E-selectin. MAPK8 was highly expressed in ox-LDL-treated HUVEC cells, and silence of MAPK8 promoted proliferation inhibited apoptosis, suppressed inflammatory responses, and decreased the levels of VCAM-1, ICAM-1, and E-selectin, over-expression of MAPK8 partially restored the functional effects of miR-130a-3p on proliferation, inflammatory responses, and the expressions of VCAM-1, ICAM-1 and E-selectin. This study indicates that miR-130a-3p may emerge as an effective target for treating AS.
据报道,微小RNA-130a-3p(miR-130a-3p)与动脉粥样硬化(AS)密切相关。本研究旨在探讨miR-130a-3p在氧化型低密度脂蛋白(ox-LDL)处理的内皮细胞(ECs)中的作用,并探索其潜在机制。通过CCK-8、EdU和流式细胞术检测ox-LDL处理的人脐静脉内皮细胞(HUVEC)的增殖和凋亡。ELISA和蛋白质印迹分析检测细胞因子的表达和蛋白质水平。进行生物信息学和双荧光素酶报告基因检测以预测和证实丝裂原活化蛋白激酶8(MAPK8)是miR-130a-3p的直接靶点,且MAPK8与miR-130a-3p呈负相关。正如预期的那样,miR-130a-3p在ox-LDL处理的HUVEC细胞中表达下调,miR-130a-3p的上调促进了ox-LDL处理的HUVEC细胞的增殖并抑制其凋亡。此外,miR-130a-3p模拟物抑制了肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)的表达,并降低了血管细胞黏附分子-1(VCAM-1)、细胞间黏附分子-1(ICAM-1)和E-选择素的蛋白质水平。MAPK8在ox-LDL处理的HUVEC细胞中高表达,沉默MAPK8可促进增殖、抑制凋亡、抑制炎症反应并降低VCAM-1、ICAM-1和E-选择素的水平,MAPK8的过表达部分恢复了miR-130a-3p对增殖、炎症反应以及VCAM-1、ICAM-1和E-选择素表达的功能作用。本研究表明,miR-130a-3p可能成为治疗AS的有效靶点。