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电离辐射对A549人非小细胞肺癌细胞中miRNA谱的改变。

Alteration of miRNA profiles by ionizing radiation in A549 human non-small cell lung cancer cells.

作者信息

Shin Sangsu, Cha Hwa Jun, Lee Eun-Mee, Lee Su-Jae, Seo Sung-Keum, Jin Hyeon-Ok, Park In-Chul, Jin Young-Woo, An Sungkwan

机构信息

Functional Genoproteome Research Centre, Konkuk University, Seoul 143-701, Korea.

出版信息

Int J Oncol. 2009 Jul;35(1):81-6.

Abstract

Ionizing radiation (IR) is widely used in cancer treatment and in biological studies. It disrupts cellular homeostasis through multiple mechanisms including changes of the expression profile of genes. Although microRNAs (miRNAs) have recently been recognized as important post-transcriptional regulators and are involved in various biological processes, whether miRNAs play any roles in the cellular response to IR, is not well examined. We investigated the profile of miRNA expression following IR in the human lung carcinoma cell line A549, and the expression profiles of IR-responsive miRNAs were confirmed by qRT-PCR. The target mRNAs of IR-responsive miRNAs were predicted with a target prediction tool. Microarray analysis identified 12 and 18 miRNAs in 20- and 40 Gy-exposed A549 cells, respectively, that exhibited more than 2-fold changes in their expression levels. Of these, four were changed in only 20-Gy-treated cells, ten only in 40-Gy-treated cells, and eight miRNAs were found to change after both treatments. qRT-PCR analysis of a subset of the miRNAs showed patterns of regulation as the microarray data, although the magnitude of the changes differed in the two data sets. Target prediction for IR-responsive miRNAs suggests that they target genes related to apoptosis, regulation of cell cycle, and DNA damage and repair. Taken together, these data suggest that miRNA expression is affected by radiation, and they may be involved in the regulation of radiation responses.

摘要

电离辐射(IR)广泛应用于癌症治疗和生物学研究。它通过多种机制破坏细胞内稳态,包括基因表达谱的改变。尽管微小RNA(miRNA)最近被认为是重要的转录后调节因子,并参与各种生物学过程,但miRNA在细胞对IR的反应中是否发挥任何作用尚未得到充分研究。我们研究了人肺癌细胞系A549在IR照射后miRNA的表达谱,并通过qRT-PCR证实了IR反应性miRNA的表达谱。使用靶标预测工具预测IR反应性miRNA的靶标mRNA。微阵列分析分别在接受20 Gy和40 Gy照射的A549细胞中鉴定出12个和18个miRNA,其表达水平变化超过2倍。其中,4个仅在接受20 Gy处理的细胞中发生变化,10个仅在接受40 Gy处理的细胞中发生变化,8个miRNA在两种处理后均发生变化。对一部分miRNA的qRT-PCR分析显示出与微阵列数据相同的调控模式,尽管两个数据集中变化的幅度有所不同。对IR反应性miRNA的靶标预测表明,它们靶向与细胞凋亡、细胞周期调控以及DNA损伤和修复相关的基因。综上所述,这些数据表明miRNA表达受辐射影响,并且它们可能参与辐射反应的调节。

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