Integrated analysis of differential miRNA and mRNA expression profiles in human radioresistant and radiosensitive nasopharyngeal carcinoma cells.
Integrated analysis of differential miRNA and mRNA expression profiles in human radioresistant and radiosensitive nasopharyngeal carcinoma cells.
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人放射抗性和放射敏感性鼻咽癌细胞差异miRNA和mRNA表达谱的综合分析
DOI：
10.1371/journal.pone.0087767
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Xiao ZQ
中科院分区：
文献类型：
--
作者：
Li XH;Qu JQ;Yi H;Zhang PF;Yi HM;Wan XX;He QY;Ye X;Yuan L;Zhu JF;Li JY;Xiao ZQ
本研究的目的是寻找与鼻咽癌放射抗性相关的miRNAs和基因，探讨鼻咽癌放射抗性发生的可能机制。我们采用基因芯片技术比较了鼻咽癌CNE2-IR细胞和鼻咽癌放射敏感细胞中miRNA和mRNA表达谱的差异，应用qRT-PCR验证了芯片数据的可靠性，采用数据库预测和miRNA及mRNA表达的反相关分析确定了miRNA靶基因，并利用生物信息学工具研究了miRNA靶基因的功能和参与的途径，构建了miRNA靶基因调控网络。我们进一步研究了miRNA-23a及其靶基因IL-8在鼻咽癌放射抗性中的作用。主要研究结果如下：(1)共鉴定出15个差异miRNAs和372个差异mRNAs，并对随机选取的8个miRNAs和9个基因验证了微阵列数据的可靠性：(2)鉴定出174个miRNA靶点，它们的大部分功能和调控途径与肿瘤的治疗耐药有关：(3)构建了一个包含375个miRNA-靶基因对的转录后调控网络，其中10个基因由6个miRNAs共同调控；(4)IL-8是miRNA-23a的直接靶点，在放射抗性鼻咽癌组织中IL-8的表达水平升高，并与miRNA-23a的表达呈负相关，miRNA-23a的基因上调和分泌IL-8的抗体中和可降低鼻咽癌细胞的辐射抗性。我们在鼻咽癌放射抗性细胞中鉴定了15个差异miRNAs和372个差异mRNAs，构建了由375对miRNA-靶基因组成的转录后调控网络，发现了6个miRNAs共同调控的10个靶基因，并通过直接靶向IL-8证实了下调的miRNA-23a参与了鼻咽癌的辐射抗性。我们的数据为进一步研究鼻咽癌辐射抗性的机制奠定了基础。
The purpose of this study was to identify miRNAs and genes involved in nasopharyngeal carcinoma (NPC) radioresistance, and explore the underlying mechanisms in the development of radioresistance. We used microarrays to compare the differences of both miRNA and mRNA expression profiles in the radioresistant NPC CNE2-IR and radiosensitive NPC CNE2 cells, applied qRT-PCR to confirm the reliability of microarray data, adopted databases prediction and anticorrelated analysis of miRNA and mRNA expression to identify the miRNA target genes, and employed bioinformatics tools to examine the functions and pathways in which miRNA target genes are involved, and construct a miRNA-target gene regulatory network. We further investigated the roles of miRNA-23a and its target gene IL-8 in the NPC radioresistance. The main findings were fourfold: (1) fifteen differential miRNAs and 372 differential mRNAs were identified, and the reliability of microarray data was validated for randomly selected eight miRNAs and nine genes; (2) 174 miRNA target were identified, and most of their functions and regulating pathways were related to tumor therapeutic resistance; (3) a posttranscriptional regulatory network including 375 miRNA-target gene pairs was constructed, in which the ten genes were coregulated by the six miRNAs; (4) IL-8 was a direct target of miRNA-23a, the expression levels of IL-8 were elevated in the radioresistant NPC tissues and showed inverse correlation with miRNA-23a expression, and genetic upregulation of miRNA-23a and antibody neutralization of secretory IL-8 could reduce NPC cells radioresistance. We identified fifteen differential miRNAs and 372 differential mRNAs in the radioresistant NPC cells, constructed a posttranscriptional regulatory network including 375 miRNA-target gene pairs, discovered the ten target genes coregulated by the six miRNAs, and validated that downregulated miRNA-23a was involved in NPC radioresistance through directly targeting IL-8. Our data form a basis for further investigating the mechanisms of NPC radioresistance.
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影响因子：
11.2
作者：
Hardee ME;Marciscano AE;Medina-Ramirez CM;Zagzag D;Narayana A;Lonning SM;Barcellos-Hoff MH
通讯作者：
Barcellos-Hoff MH
DOI：
10.1146/annurev.pathol.4.110807.092222
发表时间：
2009
期刊：
Annual review of pathology
影响因子：
--
作者：
Lee YS;Dutta A
通讯作者：
Dutta A
miR-23a-27a-24-2簇的上调诱导人类胚胎肾细胞中的caspase依赖性和非依赖性凋亡。
影响因子：
3.7
作者：
Chhabra R;Adlakha YK;Hariharan M;Scaria V;Saini N
通讯作者：
Saini N
影响因子：
3.7
作者：
Enerly E;Steinfeld I;Kleivi K;Leivonen SK;Aure MR;Russnes HG;Rønneberg JA;Johnsen H;Navon R;Rødland E;Mäkelä R;Naume B;Perälä M;Kallioniemi O;Kristensen VN;Yakhini Z;Børresen-Dale AL
通讯作者：
Børresen-Dale AL
影响因子：
6.4
作者：
Bonovich, M;Olive, M;Vinson, C
通讯作者：
Vinson, C