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基于转录组测序在人类全基因组内鉴定与癌症相关的polyadenylation和non-polyadenylationRNA

, PP. 376-386

Keywords: 多聚腺苷酸化,非多聚腺苷酸化,功能注释,高通量测序,癌症生物信息学

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Abstract:

真核生物的mRNA包括2种形式的转录本,根据它们3'端是否存在poly(A)尾巴,可以分为带poly(A)的mRNA(简写成poly(A)+mRNA)和不带poly(A)的mRNA(简写成poly(A)-mRNA).Poly(A)+mRNA的主要功能是促进蛋白质的编码,但是对poly(A)-mRNA的功能却知之甚少.而已有的研究表明,poly(A)-mRNA和双态(bimorphic)的mRNA(即包含poly(A)+mRNA又包含poly(A)-mRNA)也是基因转录的一个重要部分.本研究通过建立一个综合性的数据分析流程,首先从不同细胞系中鉴定出这些不同形式的mRNA,然后比较这些poly(A)+及poly(A)-mRNA在正常细胞系和对应的癌症细胞系中的表达差异,从而确定这些RNA转录物的潜在功能.通过生物信息学的分析表明,在正常和肿瘤细胞系中确实存在差异表达的poly(A)+和poly(A)-mRNA.对差异表达的基因进行功能富集,结果表明,这2类mRNA都富集了包括细胞周期、细胞凋亡及细胞死亡相关的功能,而这些功能已经被证明和癌症的发生和发展是密不可分的.此外,还有一类差异表达的poly(A)-mRNA富集了和翻译及翻译延长相关的功能.因此,本研究表明,poly(A)-mRNA也可能在癌症的发生和发展中发挥着重要的作用.

References

[1]  28 Wrage M, Ruosaari S, Eijk P P, et al. Genomic profiles associated with early micrometastasis in lung cancer: relevance of 4q deletion. Clin Cancer Res, 2009, 15: 1566-1574
[2]  29 Barnhart B C, Lam J C, Young R M, et al. Effects of 4E-BP1 expression on hypoxic cell cycle inhibition and tumor cell proliferation and survival. Cancer Biol Ther, 2008, 7: 1441-1449
[3]  30 She Q B, Halilovic E, Ye Q, et al. 4E-BP1 is a key effector of the oncogenic activation of the AKT and ERK signaling pathways that integrates their function in tumors. Cancer Cell, 2010, 18: 39-51
[4]  31 Collins K, Jacks T, Pavletich N P. Apoptosis: a review of programmed cell death. Toxicol Pathol, 2007, 35: 495-516
[5]  32 Zamai L, Ponti C, Mirandola P, et al. NK cells and cancer. J Immunol, 2007, 178: 4011-4016
[6]  33 Park M T, Lee S J. Cell cycle and cancer. J Biochem Mol Biol, 2003, 36: 60-65
[7]  34 Schadt E E, Linderman M D, Sorenson J, et al. Computational solutions to large-scale data management and analysis. Nat Rev Genet, 2010, 11: 647-657
[8]  35 Yang J, Yang F, Ren L, et al. Unbiased parallel detection of viral pathogens in clinical samples by use of a metagenomic approach. J Clin Microbiol, 2011, 49: 3463-3469
[9]  36 Sun L, Luo H T, Liao Q, et al. Systematic study of human long intergenic non-coding RNAs and their impact on cancer. Sci China Life Sci, 2013, 56, 324-334
[10]  37 Yu W, Gius D, Onyango P, et al. Epigenetic silencing of tumour suppressor gene p15 by its antisense RNA. Nature, 2008, 451: 202-206
[11]  38 Huarte M, Guttman M, Feldser D, et al. A large intergenic noncoding RNA induced by p53 mediates global gene repression in the p53 response. Cell, 2010, 142: 409-419
[12]  39 Esteller M. Non-coding RNAs in human disease. Nat Rev Genet, 2011, 12: 861-874
[13]  40 Prensner J R, Iyer M K, Balbin O A, et al. Transcriptome sequencing across a prostate cancer cohort identifies PCAT-1, an unannotated lincRNA implicated in disease progression. Nat Biotechnol, 2011, 29: 742-749
[14]  41 Liao Q, Xiao H, Bu D C, et al. NcFANs: a web server for functional annotation of long non-coding RNAs. Nucleic Acids Res, 2011, 39: W118-W124
[15]  42 Liao Q, Liu C N, Yuan X Y, et al. Large-scale prediction of long non-coding RNA functions in a coding-non-coding gene co-expression network. Nucleic Acids Res, 2011, 39: 3864-3878
[16]  43 Bu D C, Yu K T, Sun S, et al. NONCODE v3.0: integrative annotation of long noncoding RNAs. Nucleic Acids Res, 2012, 40: D210-D215
[17]  44 Guo X L, Gao L, Liao Q, et al. Long non-coding RNAs function annotation: a global prediction method based on bi-colored networks. Nucleic Acids Res, 2013, 41: E35
[18]  26 Landi M T, Dracheva T, Rotunno M, et al. Gene expression signature of cigarette smoking and its role in lung adenocarcinoma development and survival. PLoS ONE, 2008, 3: e1651
[19]  27 Rohrbeck A, Neukirchen J, Rosskopf M, et al. Gene expression profiling for molecular distinction and characterization of laser captured primary lung cancers. J Transl Med, 2008, 6: 69
[20]  1 Wu Q, Kim Y C, Lu J, et al. Poly A-transcripts expressed in HeLa cells. PLoS ONE, 2008, 3: e2803
[21]  2 Cheng J, Kapranov P, Drenkow J, et al. Transcriptional maps of 10 human chromosomes at 5-nucleotide resolution. Science, 2005, 308: 1149-1154
[22]  3 Katinakis P, Slater A, Burdon R. Non-polyadenylated mRNAs from eukaryotes. FEBS Lett, 1980, 116: 1-7
[23]  4 Moore M J, Proudfoot N J. Pre-mRNA processing reaches back to transcription and ahead to translation. Cell, 2009, 136: 688-700
[24]  5 Grummt I. Regulation of mammalian ribosomal gene transcription by RNA polymerase Ⅰ. Prog Nucleic Acid Re, 1998, 62: 109-154
[25]  6 Detke S, Stein J L, Stein G S. Synthesis of histone messenger RNAs by RNA polymerase Ⅱ in nuclei from S phase HeLa S3 cells. Nucleic Acids Res, 1978, 5: 1515-1528
[26]  7 Willis I M. RNA Polymerase-Iii-genes, factors and transcriptional specificity. Eur J Biochem, 1993, 212: 1-11
[27]  8 Sunwoo H, Dinger M E, Wilusz J E, et al. MEN epsilon/beta nuclear-retained non-coding RNAs are up-regulated upon muscle differentiation and are essential components of paraspeckles. Genome Res, 2009, 19: 347-359
[28]  9 Wang E T, Sandberg R, Luo S, et al. Alternative isoform regulation in human tissue transcriptomes. Nature, 2008, 456: 470-476
[29]  10 Li J B, Levanon E Y, Yoon J K, et al. Genome-wide identification of human RNA editing sites by parallel DNA capturing and sequencing. Science, 2009, 324: 1210-1213
[30]  11 Yang L, Duff M O, Graveley B R, et al. Genomewide characterization of non-polyadenylated RNAs. Genome Biol, 2011, 12: R16
[31]  12 Cheng J, Kapranov P, Drenkow J, et al. Transcriptional maps of 10 human chromosomes at 5-nucleotide resolution. Science, 2005, 308: 1149-1154
[32]  13 Rosenbloom K R, Dreszer T R, Long J C, et al. ENCODE whole-genome data in the UCSC genome browser: update 2012. Nucleic Acids Res, 2012, 40: D912-D917
[33]  14 Trapnell C, Pachter L, Salzberg S L. TopHat: discovering splice junctions with RNA-seq. Bioinformatics, 2009, 25: 1105-1111
[34]  15 Langmead B, Trapnell C, Pop M, et al. Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome Biol, 2009, 10: R25
[35]  16 Trapnell C, Williams B A, Pertea G, et al. Transcript assembly and quantification by RNA-seq reveals unannotated transcripts and isoform switching during cell differentiation. Nat biotechnol, 2010, 28: 511-515
[36]  17 Garber M, Grabherr M G, Guttman M, et al. Computational methods for transcriptome annotation and quantification using RNA-seq. Nature Methods, 2011, 8: 469-477
[37]  18 Cabili M N, Trapnell C, Goff L, et al. Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses. Genes Devel, 2011, 25: 1915-1927
[38]  19 Hanahan D, Weinberg R A. Hallmarks of cancer: the next generation. Cell, 2011, 144: 646-674
[39]  20 Hoeijmakers J H J. DNA damage, aging, and cancer. New Engl J Med, 2009, 361: 1475-1485
[40]  21 Gong X, Wu R H, Wang H W, et al. Evaluating the consistency of differential expression of microRNA detected in human cancers. Mol Cancer Ther, 2011, 10: 752-760
[41]  22 Jackson S P, Bartek J. The DNA-damage response in human biology and disease. Nature, 2009, 461: 1071-1078
[42]  23 Massagué J. G1 cell-cycle control and cancer. Nature, 2004, 432: 298-306
[43]  24 Evan G I, Vousden K H. Proliferation, cell cycle and apoptosis in cancer. Nature, 2001, 411: 342-348
[44]  25 Wang L S, Xiong Y Y, Sun Y H, et al. HLungDB: an integrated database of human lung cancer research. Nucleic Acids Res, 2010, 38: D665-D669

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