Modulation of microRNA expression in human lung cancer cells by the G9a histone methyltransferase inhibitor BIX01294.

Modulation of microRNA expression in human lung cancer cells by the G9a histone methyltransferase inhibitor BIX01294.
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DOI:
10.3892/ol.2014.2034
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发表时间:
2014-06
期刊:
影响因子:
2.9
通讯作者:
Rennert OM
Rennert OM
中科院分区:
医学4区
文献类型:
--
作者:
Pang AL;Title AC;Rennert OM

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MicroRNAs(MiRNAs)是一种小的非编码RNA,在转录后水平上调节其靶基因的表达。在癌细胞中,miRNAs根据其靶基因的生物学功能,可能具有促进或抑制肿瘤的作用。用DNA甲基化和/或组蛋白去乙酰化抑制剂处理癌细胞可以调节miRNAs的表达水平,这为表观遗传调控miRNA的表达提供了证据。然而,抑制组蛋白甲基转移酶对miRNA表达的影响还没有得到彻底的研究。本研究检测了非小细胞肺癌细胞系H1299在BIX01294处理或不处理的情况下miRNAs的表达模式。BIX01294是一种有效的G9a甲基转移酶化学抑制剂,催化组蛋白H3赖氨酸9残基的单甲基化和双甲基化。通过结合微阵列分析和实时定量聚合酶链式反应分析,鉴定出两个在BIX01294治疗后持续下调的miRNAs。结果表明,组蛋白H3甲基化调节肺癌细胞miRNA的表达,这可能为未来肺癌的化学治疗提供新的见解。
MicroRNAs (miRNAs) are small non-coding RNAs that regulate the expression of their target genes at the post-transcriptional level. In cancer cells, miRNAs, depending on the biological functions of their target genes, may have a tumor-promoting or -suppressing effect. Treatment of cancer cells with inhibitors of DNA methylation and/or histone deacetylation modulates the expression level of miRNAs, which provides evidence for epigenetic regulation of miRNA expression. The consequences of inhibition of histone methyltransferase on miRNA expression, however, have not been thoroughly investigated. The present study examined the expression pattern of miRNAs in the non-small cell lung cancer cell line, H1299 with or without treatment of BIX01294, a potent chemical inhibitor of G9a methyltransferase that catalyzes the mono-and di-methylation of the lysine 9 residue of histone H3. By coupling microarray analysis with quantitative real-time polymerase chain reaction analysis, two miRNAs were identified that showed consistent downregulation following BIX01294 treatment. The results indicate that histone H3 methylation regulates miRNA expression in lung cancer cells, which may provide additional insight for future chemical treatment of lung cancer.
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