长链非编码 RNA HCG11 通过靶向 miR-144-3p/FOXF1 轴调控动脉粥样硬化中血管平滑肌细胞的增殖和凋亡。
LncRNA HCG11 regulates proliferation and apoptosis of vascular smooth muscle cell through targeting miR-144-3p/FOXF1 axis in atherosclerosis.
机构信息
Department of Clinical laboratory, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China.
Department of Clinical Laboratory, Weapon Industry 206 Hospital, Xi'an, Shaanxi, 710061, China.
出版信息
Biol Res. 2020 Oct 2;53(1):44. doi: 10.1186/s40659-020-00306-2.
BACKGROUND
Atherosclerosis (AS) is the main pathological basis of coronary heart disease, cerebral infarction and peripheral vascular disease, which seriously endanger people's life and health. In recent years, long non-coding RNA (lncRNA) has been found to be involved in gene expression regulation, but the research on AS is still in the initial stage. In this study, we mainly studied the role of HCG11 in patients with AS. Quantitative Real-time Polymerase Chain Reaction (QRT-PCR) was used to detect the expression of HCG11 and miR-144 in the serum of AS patients and healthy volunteers. Oxidation Low Lipoprotein (Ox-LDL), interleukin-6 (IL-6) and tumor necrosis factor α (TNF α) radiation were used to establish human vascular smooth muscle cells (VSMCs) in vitro model. Cell proliferation was determined by Cell Counting Kit-8 (CCK-8) assay. The apoptosis rate was determined by flow cytometry (FACS) and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL) staining. The expression levels of Forkhead box protein F1 (FOXF1), B cell lymphoma-2 (Bcl-2) and BCL2-Associated X (Bax) were detected by qRT-PCR. Luciferase gene reporter and RNA pull down experiments confirmed the relationship between HCG11 and miR-144, miR-144 and FOXF1.
RESULTS
This study showed that HCG11 was significantly upregulated in patients with AS, while miR-144 was down-regulated in patients with AS. Ox-LDL and IL-6 in VSMCs induced up-regulation of HCG11 and down-regulation of miR-144. Overexpression of HCG11 promoted the proliferation and inhibited apoptosis of VSMCs. Luciferase gene reporter gene assay showed that HCG11 could bind to miR-144, and miR-144 could bind to FOXF1. Overexpression of miR-144 reversed the effect of HCG11 on VSMCs.
CONCLUSIONS
LncRNA HCG11 regulates proliferation and apoptosis of vascular smooth muscle cell through targeting miR-144-3p/FOXF1 axis.
背景
动脉粥样硬化（AS）是冠心病、脑梗死和外周血管病的主要病理基础，严重危害人们的生命健康。近年来，长链非编码 RNA（lncRNA）被发现参与基因表达调控，但 AS 的研究仍处于起步阶段。本研究主要探讨 HCG11 在 AS 患者中的作用。采用实时荧光定量聚合酶链反应（QRT-PCR）检测 AS 患者和健康志愿者血清中 HCG11 和 miR-144 的表达。用氧化型低密度脂蛋白（Ox-LDL）、白细胞介素 6（IL-6）和肿瘤坏死因子α（TNFα）辐射建立人血管平滑肌细胞（VSMCs）体外模型。采用细胞计数试剂盒-8（CCK-8）法测定细胞增殖。用流式细胞术（FACS）和末端脱氧核苷酸转移酶介导的 dUTP-生物素 nick 末端标记（TUNEL）染色法测定细胞凋亡率。用 qRT-PCR 检测叉头框蛋白 F1（FOXF1）、B 细胞淋巴瘤-2（Bcl-2）和 BCL2 相关 X（Bax）的表达水平。荧光素酶基因报告和 RNA 下拉实验证实了 HCG11 与 miR-144、miR-144 与 FOXF1 之间的关系。
结果
本研究表明，AS 患者 HCG11 表达明显上调，AS 患者 miR-144 表达下调。VSMCs 中 Ox-LDL 和 IL-6 诱导 HCG11 上调和 miR-144 下调。HCG11 过表达促进 VSMCs 增殖，抑制细胞凋亡。荧光素酶基因报告基因检测表明，HCG11 可与 miR-144 结合，miR-144 可与 FOXF1 结合。miR-144 过表达逆转了 HCG11 对 VSMCs 的作用。
结论
lncRNA HCG11 通过靶向 miR-144-3p/FOXF1 轴调节血管平滑肌细胞的增殖和凋亡。
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