The suppression of ox-LDL-induced inflammatory cytokine release and apoptosis of HCAECs by long non-coding RNA-MALATI via regulating microRNA-155/SOCS1 pathway
The suppression of ox-LDL-induced inflammatory cytokine release and apoptosis of HCAECs by long non-coding RNA-MALATI via regulating microRNA-155/SOCS1 pathway
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DOI：
10.1016/j.numecd.2018.06.017
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发表时间：
2018-11-01
影响因子：
3.9
通讯作者：
Chen, X.
中科院分区：
文献类型：
--
作者：
Li, S.;Sun, Y.;Chen, X.
背景：动脉粥样硬化是一种慢性炎症性疾病。越来越多的证据表明，长链非编码RNA（lncRNA）和microRNA已成为动脉粥样硬化的关键调节因子;然而，它们是否在这个问题上存在串扰仍然难以捉摸。在这里，我们研究了lncRNA-MALATI和miR-155之间的潜在关联的调节动脉粥样硬化。方法：采用定量实时PCR评估MALATI，IL-6和IL-8的表达。进行ELISA以测量IL-6和IL-8的分泌。MTT法检测人冠状动脉内皮细胞增殖情况。流式细胞仪检测细胞凋亡。Western blot检测HCAECs中炎症相关蛋白的表达及STAT 1、STAT 3的磷酸化水平。结果：ox-LDL诱导HCAECs释放促炎细胞因子，并诱导HCAECs凋亡，同时MALATI表达上调。敲低MALATI促进ox-LDL诱导的细胞因子释放和HCAECs凋亡。通过双荧光素酶测定法确认MALATI序列中miR-155的结合位点。此外，miR-155抑制显著抑制ox-LDL介导的HCAECs炎症和凋亡通过SOCS 1。结论：本研究揭示了MALATI通过增加miR-155和SOCS 1的表达，抑制炎症因子的释放和细胞凋亡，从而抑制JAK-STAT信号通路。因此，MALAT 1/miR-155/SOCS 1轴的调节可能减轻动脉粥样硬化中持续存在的炎症。(C)2018年由Elsevier B. V.代表意大利糖尿病学会、意大利动脉粥样硬化研究学会、意大利人类营养学会和费德里科二世大学临床医学和外科系发表。
Background: Atherosclerosis is a chronic inflammatory disease. Accumulating evidence suggests that long non-coding RNAs (lncRNAs) and microRNAs have emerged as critical regulators of atherosclerosis; however, whether they have crosstalk on this issue remains elusive. Here, we investigated the potential associations between lncRNA-MALAT1 and miR-155 on the regulation of atherosclerosis.Methods: Quantitative real-time PCR was employed to assess the expression of MALATI, IL-6 and IL-8. ELISA was performed to measure the secretion of IL-6 and IL-8. MTT assay was used to determine the proliferation of Human Coronary Artery Endothelial Cells (HCAECs). Flow cytometry was used to measure the cell apoptosis. Western blot was used to assess the expression of apoptosis-related proteins and the phosphorylation of STAT1 and STAT3.Results: We found that the pro-inflammatory cytokine release and the apoptosis of HCAECs were elevated upon ox-LDL treatment, while MALATI expression was also up regulated. Knocking down of MALATI boosted ox-LDL-induced cytokine release and apoptosis of HCAECs. The binding site of miR-155 in MALATI sequence was confirmed by dual luciferase assay. Furthermore, miR-155 inhibition significantly repressed ox-LDL mediated inflammation and apoptosis of HCAECs via SOCS1. At last, we found that MALATI could suppress the inflammatory cytokine release and cell apoptosis via sponging miR-155 to increase SOCS1 level, which in turn restrained JAK-STAT pathway.Conclusion: In summary, this study revealed the mechanisms by which MALATI worked as a putative atherosclerosis suppressor via miR-155 and SOCS1. Therefore, modulation of MALAT1/miR-155/ SOCS1 axis might alleviate the inflammation persisted in atherosclerosis. (C) 2018 Published by Elsevier B.V. on behalf of The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University.