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综合分析表明增强人的长链非编码RNA的调节作用在肺腺癌
  • ISSN号:1673-8527
  • 期刊名称:《遗传学报:英文版》
  • 时间:0
  • 分类:Q522[生物学—生物化学] Q753[生物学—分子生物学]
  • 作者机构:[1]State Key Laboratory of Medical Genomics, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai 200031, China, [2]State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai 200433, China
  • 相关基金:ACKNOWLEDGMENTS We are grateful to all of the lung adenocarcinoma patients described herein for their contributions to this study. We thank Young Tae Kim and his colleagues for generating and providing transcriptome sequencing data of the patients. We also thank Laurence D. Hurst and John L. Rinn for critical reading of the manuscript. This work was supported by the National Basic Research Program of China (No. 2011CB510100), and the National Natural Science Foundation of China (No. 81030015).
中文摘要:

虽然是一个累积升值,长链非编码RNA的关键作用(使lincRNAs)在不同的细胞过程中发挥,我们如何在癌症的功能使lincRNAs知识仍然稀疏。在这里,我们提出一个RNA序列的转录谱的肺腺癌和正常同行的综合景观解开使lincRNAs基因调控规律。与相邻的蛋白质编码基因之间的共表达以前的研究结果相一致,使lincRNAs是典型的有限与邻近基因的表达,而在癌组织和正常组织中发现。通过建立一个基于相关基因表达的数学模型,我们区分一个额外的子集称为“使lincRNAs调控使lincRNAs”,代表其在基因调控中的主导作用。监管使lincRNAs数癌显著高于正常组织,且大多正调控蛋白编码基因的反式。利用基因功能验证,确定监管,lincRNA,Gass,影响其预测蛋白质编码的目标。此外,我们发现了数百个差异表达的调控使lincRNAs与一些癌症相关的使lincRNAs夹杂。我们的综合分析显示,提高监管效果,为使lincRNAs调控使lincRNAs在肺腺癌中起关键作用的研究资源。

英文摘要:

Although there is an accumulating appreciation of the key roles that long intergenic non-coding RNAs (lincRNAs) play in diverse cellular processes, our knowledge of how lincRNAs function in cancer remains sparse. Here, we present a comprehensive landscape of RNA-seq transcriptome profiles of lung adenocarcinomas and their paired normal counterparts to unravel gene regulation rules of lincRNAs. Consistent with previous findings of co-expression between neighboring protein-coding genes, lincRNAs were typically co-expressed with their neighboring genes, which was found in both cancerous and normal tissues. By building a mathematical model based on correlated gene expression, we distinguished an additional subset of lincRNAs termed "regulatory lincRNAs", representing their dominant roles in gene regulation. The number of regulatory lincRNAs was significantly higher in cancerous compared to normal tissues, and most of them positively regulated protein-coding genes in trans. Functional validation, using knockdown, determined that regulatory lincRNA, GASS, affected its predicted protein-coding targets. Moreover, we discovered hundreds of differentially expressed regulatory lincRNAs with inclusion of some cancer-associated lincRNAs. Our integrated analysis reveals enhanced regulatory effects of lincRNAs and provides a resource for the study of regulatory lincRNAs that play critical roles in lung adenocarcinoma.

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期刊信息
  • 《遗传学报:英文版》
  • 北大核心期刊(2004版)
  • 主管单位:中国科学院
  • 主办单位:中国科学院遗传与发育生物学研究所 中国遗传学会
  • 主编:薛勇彪
  • 地址:北京市安定门外大屯路中科院遗传发育所
  • 邮编:100101
  • 邮箱:ycxb@genetics.ac.cn
  • 电话:010-64807669
  • 国际标准刊号:ISSN:1673-8527
  • 国内统一刊号:ISSN:11-5450/R
  • 邮发代号:2-819
  • 获奖情况:
  • 1996年获中科院优秀期刊二等奖,1997年获全国优秀期刊三等奖,200年获中科院优秀期刊二等奖
  • 国内外数据库收录:
  • 俄罗斯文摘杂志,美国化学文摘(网络版),英国农业与生物科学研究中心文摘,波兰哥白尼索引,荷兰文摘与引文数据库,荷兰医学文摘,美国生物医学检索系统,美国科学引文索引(扩展库),美国生物科学数据库,英国动物学记录,日本日本科学技术振兴机构数据库,中国中国科技核心期刊,中国北大核心期刊(2004版),中国北大核心期刊(2000版)
  • 被引量:17519