李 峰,张 超.良性脑膜瘤中IL-1β对NF2基因甲基化调控的作用研究[J].肿瘤学杂志,2019,25(2):116-120. |
良性脑膜瘤中IL-1β对NF2基因甲基化调控的作用研究 |
IL-1β Regulates NF2 Gene Methylation in Benign Meningioma |
投稿时间:2018-03-06 |
DOI:10.11735/j.issn.1671-170X.2019.02.B008 |
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中文关键词: 良性脑膜瘤 IL-1β NF2 甲基化 甲基化转移酶 |
英文关键词:benign meningioma IL-1β NF2 methylation DNMTs |
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中文摘要: |
摘 要:[目的] 探讨良性脑膜瘤中炎症因子IL-1β在NF2甲基化中的作用及调控机制。[方法] 利用2个脑膜瘤患者手术后的标本做原代细胞培养,不同浓度IL-1β(0,0.2, 0.4,0.8,1.0,10ng/ml)处理细胞,利用RT-PCR和Western blot检测NF2、merlin和DNMTs的表达,利用甲基化特异性PCR检测NF2启动子甲基化水平。通过共同添加IL-1β和DNMT抑制剂或siRNA,观察IL-1β与NF2甲基化的关系。 [结果] IL-1β能促进脑膜瘤细胞的增殖。RT-PCR及Western blot结果显示,IL-1β能降低脑膜瘤细胞NF2和merlin的表达。IL-1β能诱导脑膜瘤细胞NF2启动子甲基化;同时IL-1β能增加脑膜瘤细胞中DNMT1的表达,而IL-1β诱导脑膜瘤细胞的NF2启动子甲基化可以被DNMT抑制剂和siRNA抑制。[结论] IL-1β通过DNMT1诱导NF2基因启动子的甲基化,这种甲基化可以下调NF2基因的转录。抑制DNMTs可以考虑作为调控NF2表达和和抑制脑膜瘤发展的治疗靶点。 |
英文摘要: |
Abstract:[Objective] To investigate the role of IL-1β in regulating the NF2 gene methylation in benign meningioma. [Methods] The primary meningioma cells obtained from 2 patients were cultured,and the cells were treated with IL-1β at different concentrations(0,0.2,0.4,0.8,1.0,10ng/ml). The mRNA and protein expressions of NF2,merlin and DNMT were detected by RT-PCR and Western blot,respectively. The methylation level of NF2 promoter was detected by MS-PCR. The relationship between IL-1β and NF2 methylation was observed by co-treatment with IL-1β and DNMT inhibitors or siRNA. [Results] IL-1β promoted the proliferation of meningioma cells. RT-PCR and Western blot results showed that IL-1β reduced the expression of NF2 and Merlin in meningioma cells. IL-1β induced methylation of NF2 gene promoter in meningioma cells,and increased the expression of DNMT1 in meningioma cells,while this effect was inhibited by DNMT inhibitors and siRNA. [Conclusion] IL-1β induces methylation of NF2 gene promoter through DNMT1,which can downregulate the transcription of NF2 gene. Inhibition of DNMTs might be used as a therapeutic approach for regulating the expression of NF2 and inhibiting the development of meningioma. |
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