Department of Cardiology, Huaihe Hospital of Henan University, No. 8, Baobei Road, Gulou District, Kaifeng, 475000, China.
Department of Cardiology, Huaihe Hospital of Henan University, No. 8, Baobei Road, Gulou District, Kaifeng, 475000, China.
Biomed Pharmacother. 2018 Jan;97:1078-1085. doi: 10.1016/j.biopha.2017.11.052. Epub 2017 Nov 10.
Plenty of lncRNAs and microRNAs have been identified to be critical mediators in the progression of atherosclerosis (AS). Myocardial infarction-associated transcript (MIAT) were aberrantly high expressed and closely associated with the pathogenesis of AS. However, its molecular mechanism has not been well characterized.
The expression patterns of MIAT and microRNA-181b (miR-181b) in clinical samples and cells were measured by RT-qPCR assays. Luciferase reporter assay and RIP assays were used to manifest the potential interaction between MIAT, miR-181b and signal transducer and activator of transcription 3 (STAT3). Cell Counting Kit-8 (CCK-8), Propidium Iodide (PI) staining, Terminal dexynucleotidyl transferase(TdT)-mediated dUTP nick end labeling (TUNEL) and western blot assays were carried out to detect cell proliferation, cell cycle distribution, apoptosis, and STAT3 protein level, respectively.
MIAT expression was up-regulated and miR-181b expression was down-regulated in AS patients serum and oxidized low-density lipoprotein (ox-LDL) induced AS cells model. MIAT facilitated cell proliferation, accelerated cell cycle progression and inhibited apoptosis in ox-LDL-induced AS cell lines, while this effect was partly reversed by miR-181b overexpression. Moreover, MIAT enhanced STAT3 expression through sequestering miR-181b as a molecular sponge. Furthermore, MiR-181b hindered cell growth, induced cell cycle arrest and promoted apoptosis by directly targeting STAT3.
MIAT performed as an induction factor of AS by regulating miR-181b/STAT3 axis in ox-LDL-induced AS cell lines, offering a new insight into the potential application of MIAT in AS treatment.
大量的长链非编码 RNA 和 microRNA 已被鉴定为动脉粥样硬化（AS）进展的关键介质。心肌梗死相关转录物（MIAT）表达异常升高，与 AS 的发病机制密切相关。然而，其分子机制尚未得到很好的描述。
通过 RT-qPCR 测定临床样本和细胞中 MIAT 和 microRNA-181b（miR-181b）的表达模式。荧光素酶报告基因测定和 RIP 测定用于显示 MIAT、miR-181b 和信号转导和转录激活因子 3（STAT3）之间的潜在相互作用。细胞计数试剂盒-8（CCK-8）、碘化丙啶（PI）染色、末端脱氧核苷酸转移酶（TdT）介导的 dUTP 缺口末端标记（TUNEL）和 Western blot 测定分别用于检测细胞增殖、细胞周期分布、细胞凋亡和 STAT3 蛋白水平。
在 AS 患者血清和氧化型低密度脂蛋白（ox-LDL）诱导的 AS 细胞模型中，MIAT 表达上调，miR-181b 表达下调。MIAT 促进 ox-LDL 诱导的 AS 细胞系中的细胞增殖，加速细胞周期进程并抑制细胞凋亡，而 miR-181b 过表达部分逆转了这种作用。此外，MIAT 通过作为分子海绵来结合 miR-181b 来增强 STAT3 表达。此外，miR-181b 通过直接靶向 STAT3 来阻碍细胞生长、诱导细胞周期停滞和促进细胞凋亡。
MIAT 通过调节 ox-LDL 诱导的 AS 细胞系中的 miR-181b/STAT3 轴作为 AS 的诱导因子，为 MIAT 在 AS 治疗中的潜在应用提供了新的见解。
