Long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was reported to be related to atherosclerosis (AS) progression. However, the underlying mechanism of MALAT1 in AS remains unknown. Quantitative real-time polymerase chain reaction was performed to detect the expression of MALAT1 and miR-330-5p. Western blot was applied to assess the protein levels of cluster of differentiation 36, interleukin-1β, interleukin-6 and tumor necrosis factor-α, phosphorylation of nuclear factor kappa-B inhibitor alpha and phosphorylation of p65. Flow cytometry assay, cell counting kit 8 assay, triglyceride, and total cholesterol detection assays were used to detect the apoptosis, viability, and lipid indexes of THP-1 macrophages-derived foam cells. Online database starbasev2.0 was used to predict the binding sequences between MALAT1 and miR-330-5p and it was verified by dual-luciferase reporter system and RNA immunoprecipitation assay. Besides, an AS mice model was used to evaluate the effect of MALAT1 in vivo. As a result, MALAT1 was overexpressed, whereas miR-330-5p was downregulated in THP-1 macrophages-derived foam cells. MiR-330-5p was a target of MALAT1. MALAT1 depletion inhibited cell formation, apoptosis, and inflammation in THP-1 macrophages-derived foam cells. Besides, MALAT1 overexpression promoted the inflammation in AS mice model, which promoted the pathogenesis of AS. Furthermore, miR-330-5p regulated the nuclear factor kappa light chain enhancer of activated B cells (NF-κB) pathway in THP-1 macrophages-derived foam cells. Moreover, MALAT1 regulated NF-κB signal pathway to mediate the pathogenesis of AS by sponging miR-330-5p. MALAT1 sponges miR-330-5p to activate NF-κB signal pathway in THP-1 macrophages-derived foam cells. This finding may provide a novel biomarker for AS diagnosis.

中文翻译：

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长非编码 RNA MALAT1 通过 miR-330-5p/NF-κB 信号通路调节动脉粥样硬化的进展。


据报道，长非编码 RNA 转移相关肺腺癌转录物 1 (MALAT1) 与动脉粥样硬化 (AS) 进展相关。然而，MALAT1 在 AS 中的潜在机制仍不清楚。实时定量聚合酶链反应检测MALAT1和miR-330-5p的表达。采用Western blot检测分化簇36、白介素1β、白细胞介素6、肿瘤坏死因子-α的蛋白水平、核因子κ-B抑制剂α的磷酸化和p65的磷酸化。采用流式细胞术、细胞计数试剂盒8法、甘油三酯和总胆固醇检测法检测THP-1巨噬细胞来源的泡沫细胞的凋亡、活力和脂质指标。利用在线数据库starbasev2.0预测MALAT1与miR-330-5p之间的结合序列，并通过双荧光素酶报告系统和RNA免疫沉淀实验进行验证。此外，还使用AS小鼠模型来评估MALAT1的体内作用。结果，在 THP-1 巨噬细胞衍生的泡沫细胞中，MALAT1 过度表达，而 miR-330-5p 下调。 MiR-330-5p 是 MALAT1 的靶标。 MALAT1 缺失抑制了 THP-1 巨噬细胞衍生的泡沫细胞的细胞形成、细胞凋亡和炎症。此外，MALAT1过表达促进了AS小鼠模型的炎症反应，从而促进了AS的发病。此外，miR-330-5p 调节 THP-1 巨噬细胞衍生的泡沫细胞中活化 B 细胞核因子 kappa 轻链增强子 (NF-κB) 通路。此外，MALAT1通过海绵miR-330-5p调节NF-κB信号通路介导AS的发病机制。 MALAT1 海绵 miR-330-5p 激活 THP-1 巨噬细胞衍生的泡沫细胞中的 NF-κB 信号通路。 这一发现可能为 AS 诊断提供新的生物标志物。