Overexpression of the long noncoding RNA NEAT1 protects against As2O3-induced injury of cardiomyocyte by inhibiting the miR-124/NF-κB signaling pathway
Overexpression of the long noncoding RNA NEAT1 protects against As2O3-induced injury of cardiomyocyte by inhibiting the miR-124/NF-κB signaling pathway
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DOI：
10.26355/eurrev_202002_20195
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发表时间：
2020-01-01
影响因子：
3.3
通讯作者：
Li, J-J
中科院分区：
文献类型：
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作者：
Chen, X-X;Jiang, Y. J.;Li, J-J
目的：三氧化二砷(As_2O_3)近年来在治疗急性早幼粒细胞白血病等恶性肿瘤方面疗效显著。然而，越来越多的研究发现，三氧化二砷的心脏毒性增加，限制了其在临床上的广泛应用。本研究旨在探讨三氧化二砷对心肌细胞损伤的分子机制。材料与方法：采用四甲基偶氮唑盐比色法检测三氧化二砷对心肌细胞的损伤作用。RT-PCR检测NEAT1和miR-124的表达水平。通过细胞转染检测NEAT1和miR-124在As_2O_3诱导的H9c2细胞损伤中的作用。炎症因子的表达水平。用Western印迹法检测As_2O_3作用下H9c2细胞的凋亡基因和核转录因子-kappaB信号。荧光素酶分析检测NEAT1与miR-124的直接相互作用。结果：NEAT1过表达可减轻As2O3对H9c2细胞的损伤作用。IL-1β、IL-6水平。NEAT1过表达后，肿瘤坏死因子-α表达上调。此外，荧光素酶检测结果表明，NEAT1与miR-124直接相互作用。沉默miR-124通过抑制NF-kappa B信号通路，显著提高As2O_3作用下H9c2细胞的存活率。此外，过表达NEAT1可显著提高H9c2细胞在三氧化二砷作用下的存活率，而miR-124可逆转这一作用。最后，NEAT1通过抑制miR-124来调节H9c2细胞As_2O_3损伤。结论：根据实验结果，我们发现长非编码RNA NEAT1通过抑制miR-124/NF-kappa B信号通路，调节炎性因子的表达，从而保护心肌细胞免受As2O3的损伤。这为As_2O_3心肌细胞损伤提供了一种新的潜在的治疗策略。
OBJECTIVE: Arsenic trioxide (As2O3) an evident effect in the treatment of acute promyelocytic leukemia and other malignant tumors in recent years. However, more and more studies have found that the cardiac toxicity of As2O3 was increased, limiting its wide clinical application. This study aims to explore the molecule mechanisms of As2O3 on cardiomyocyte injury.MATERIALS AID METHODS: The cardiomyocyte injury under As(2)O(3 )was detected by MTT assay. The levels of NEAT1 and miR-124 were examined by RT-PCR. The functions of NEAT1 and miR-124 at H9c2 cell injury under As2O3 were detected by cell transfection of the overexpression or repression. The expression levels of inflammation factors. apoptosis genes and NF-kappa B signals were measured by Western blot in H9c2 cell lines under As2O3. The luciferase assay detected the direct interaction between NEAT1 and miR-124.RESULTS: The overexpression of NEAT1 decreased the H9c2 cells injury under As2O3. The levels of IL-1 beta, IL-6. TNF-alpha were upregulated after NEAT1 overexpression. Moreover, the luciferase assay results showed NEAT1 was directly interacting with miR-124. Silencing of miR-124 significantly increased the H9c2 cell survival under As2O3 by repressing NF-kappa B signaling pathway. Furthermore, the overexpression of NEAT1 markedly increased H9c2 cells survival under As2O3, while the miR-124 could reverse the effects. Finally, NEAT1 regulated the H9c2 cells As2O3 injury by repressing the miR-124. NF-kappa B expressions and inflammatory response.CONCLUSIONS: According to the results, we found that long non-coding RNA NEAT1 regulated the expression of inflammatory factors to protect cardiomyocytes from As2O3 damage by inhibiting miR-124/NF-kappa B signaling pathway. It provides a novel potential treatment strategy for As2O3 cardiomyocytes injury.