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Research Article

利用RNA-seq数据鉴定和分析卵巢浆液性囊腺瘤中的RNA编辑事件

卷 21, 期 3, 2021

发表于: 11 February, 2021

页: [258 - 269] 页: 12

弟呕挨: 10.2174/1566523221666210211111324

价格: $65

摘要

背景：最近的研究揭示了灵长类动物中成千上万的A-to-I RNA编辑事件。这些事件与多种癌症的发生发展密切相关，但这些事件在卵巢癌中的起源和一般功能尚不完全清楚。 目的：从RNA编辑的角度进一步确定卵巢癌的分子机制。 方法：在这里，我们使用无snp RNA编辑识别工具包(SPRINT)来检测RNA编辑位点。然后对这些编辑站点进行注释，并进行相关功能分析。 结果：在本研究中，每个样本共检测到约170万RES，其中98%的位点为A-to-G编辑位点，主要分布在非编码区。在CDS区检测到超过1000个A- to- g RES，其中近700个可能导致氨基酸变化。我们的结果还显示，3''UTR区域的编辑可以影响miRNA靶点的结合。我们预测了A-to-I RNA编辑位点引起的miRNA-mRNA相互作用改变的网络。我们还筛选了卵巢癌与邻近正常组织之间的差异RNA编辑位点。然后，我们对包含这些差异RNA编辑位点的基因进行了GO和KEGG途径富集分析。最后，我们鉴定了卵巢癌样本中潜在的RNA编辑异常事件。 结论：本研究系统地识别和分析了卵巢癌中RNA编辑事件，为探索RNA编辑在卵巢癌中的调控机制及其功能奠定了基础。

关键词: RNA编辑，卵巢癌，A-to-I，编辑水平，miRNA，综合分析

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[1]
Farajollahi S, Maas S. Molecular diversity through RNA editing: a balancing act. Trends Genet 2010; 26(5): 221-30.
[http://dx.doi.org/10.1016/j.tig.2010.02.001] [PMID: 20395010]
[2]
Bass BL. RNA editing by adenosine deaminases that act on RNA. Annu Rev Biochem 2002; 71(1): 817-46.
[http://dx.doi.org/10.1146/annurev.biochem.71.110601.135501] [PMID: 12045112]
[3]
Nishikura K. Functions and regulation of RNA editing by ADAR deaminases. Annu Rev Biochem 2010; 79: 321-49.
[http://dx.doi.org/10.1146/annurev-biochem-060208-105251] [PMID: 20192758]
[4]
Zinshteyn B, Nishikura K. Adenosine-to-inosine RNA editing. Wiley Interdiscip Rev Syst Biol Med 2009; 1(2): 202-9.
[http://dx.doi.org/10.1002/wsbm.10] [PMID: 20835992]
[5]
Peng Z, Cheng Y, Tan BCM, et al. Comprehensive analysis of RNA-Seq data reveals extensive RNA editing in a human transcriptome. Nat Biotechnol 2012; 30(3): 253-60.
[http://dx.doi.org/10.1038/nbt.2122] [PMID: 22327324]
[6]
Tan MH, Li Q, Shanmugam R, et al. Dynamic landscape and regulation of RNA editing in mammals. Nature 2017; 550(7675): 249-54.
[http://dx.doi.org/10.1038/nature24041] [PMID: 29022589]
[7]
Maas S, Kawahara Y, Tamburro KM, Nishikura K. A-to-I RNA editing and human disease. RNA Biol 2006; 3(1): 1-9.
[http://dx.doi.org/10.4161/rna.3.1.2495] [PMID: 17114938]
[8]
Han L, Diao L, Yu S, et al. The genomic landscape and clinical relevance of A-to-I RNA editing in human cancers. Cancer Cell 2015; 28(4): 515-28.
[http://dx.doi.org/10.1016/j.ccell.2015.08.013] [PMID: 26439496]
[9]
Moran B, Butler ST, Creevey CJ. Comparison and characterisation of mutation calling from whole exome and RNA sequencing data for liver and muscle tissue in lactating holstein cows divergent for fertility. bioRxiv 2017; 101733.
[http://dx.doi.org/10.1101/101733]
[10]
Zhu S, Xiang JF, Chen T, Chen LL, Yang L. Prediction of constitutive A-to-I editing sites from human transcriptomes in the absence of genomic sequences. BMC Genomics 2013; 14(1): 206.
[http://dx.doi.org/10.1186/1471-2164-14-206] [PMID: 23537002]
[11]
Blanc V, Park E, Schaefer S, et al. Genome-wide identification and functional analysis of Apobec-1-mediated C-to-U RNA editing in mouse small intestine and liver. Genome Biol 2014; 15(6): R79.
[http://dx.doi.org/10.1186/gb-2014-15-6-r79] [PMID: 24946870]
[12]
Danecek P, Nellåker C, McIntyre RE, et al. High levels of RNA-editing site conservation amongst 15 laboratory mouse strains. Genome Biol 2012; 13(4): 26.
[http://dx.doi.org/10.1186/gb-2012-13-4-r26] [PMID: 22524474]
[13]
Gu T, Buaas FW, Simons AK, Ackert-Bicknell CL, Braun RE, Hibbs MA. Canonical A-to-I and C-to-U RNA editing is enriched at 3'UTRs and microRNA target sites in multiple mouse tissues. PLoS One 2012; 7(3): e33720.
[http://dx.doi.org/10.1371/journal.pone.0033720] [PMID: 22448268]
[14]
Lagarrigue S, Hormozdiari F, Martin LJ, et al. Limited RNA editing in exons of mouse liver and adipose. Genetics 2013; 193(4): 1107-15.
[http://dx.doi.org/10.1534/genetics.112.149054] [PMID: 23410828]
[15]
Ramaswami G, Zhang R, Piskol R, et al. Identifying RNA editing sites using RNA sequencing data alone. Nat Methods 2013; 10(2): 128-32.
[http://dx.doi.org/10.1038/nmeth.2330] [PMID: 23291724]
[16]
Nishikura K. A-to-I editing of coding and non-coding RNAs by ADARs. Nat Rev Mol Cell Biol 2016; 17(2): 83-96.
[http://dx.doi.org/10.1038/nrm.2015.4] [PMID: 26648264]
[17]
Rueter SM, Dawson TR, Emeson RB. Regulation of alternative splicing by RNA editing. Nature 1999; 399(6731): 75-80.
[http://dx.doi.org/10.1038/19992] [PMID: 10331393]
[18]
Chigaev M, Yu H, Samuels DC, et al. Genomic positional dissection of RNA Editomes in tumor and normal samples. Front Genet 2019; 10: 211.
[http://dx.doi.org/10.3389/fgene.2019.00211] [PMID: 30949194]
[19]
Peng X, Xu X, Wang Y, et al. A-to-I RNA editing contributes to proteomic diversity in cancer. Cancer cell 2018; 33(5): 817-28.
[http://dx.doi.org/10.1016/j.ccell.2018.03.026] [PMID: 29706454]
[20]
Maas S, Patt S, Schrey M, Rich A. Underediting of glutamate receptor GluR-B mRNA in malignant gliomas. Proc Natl Acad Sci USA 2001; 98(25): 14687-92.
[http://dx.doi.org/10.1073/pnas.251531398] [PMID: 11717408]
[21]
Cenci C, Barzotti R, Galeano F, et al. Down-regulation of RNA editing in pediatric astrocytomas: ADAR2 editing activity inhibits cell migration and proliferation. J Biol Chem 2008; 283(11): 7251-60.
[http://dx.doi.org/10.1074/jbc.M708316200] [PMID: 18178553]
[22]
Ishiuchi S, Tsuzuki K, Yoshida Y, et al. Blockage of Ca(2+)-permeable AMPA receptors suppresses migration and induces apoptosis in human glioblastoma cells. Nat Med 2002; 8(9): 971-8.
[http://dx.doi.org/10.1038/nm746] [PMID: 12172541]
[23]
Paz N, Levanon EY, Amariglio N, et al. Altered adenosine-to-inosine RNA editing in human cancer. Genome Res 2007; 17(11): 1586-95.
[http://dx.doi.org/10.1101/gr.6493107] [PMID: 17908822]
[24]
Shah SP, Morin RD, Khattra J, et al. Mutational evolution in a lobular breast tumour profiled at single nucleotide resolution. Nature 2009; 461(7265): 809-13.
[http://dx.doi.org/10.1038/nature08489] [PMID: 19812674]
[25]
Zilberman DE, Safran M, Paz N, et al. Does RNA editing play a role in the development of urinary bladder cancer? Urol Oncol 2011; 29(1): 21-6. [C].
[http://dx.doi.org/10.1016/j.urolonc.2008.11.006] [PMID: 19186082]
[26]
Beghini A, Ripamonti CB, Peterlongo P, et al. RNA hyperediting and alternative splicing of hematopoietic cell phosphatase (PTPN6) gene in acute myeloid leukemia. Hum Mol Genet 2000; 9(15): 2297-304.
[http://dx.doi.org/10.1093/oxfordjournals.hmg.a018921] [PMID: 11001933]
[27]
Han J, An O, Hong H, et al. Suppression of adenosine-to-inosine (A-to-I) RNA editome by death associated protein 3 (DAP3) promotes cancer progression. Sci Adv 2020; 6(25): eaba5136.
[http://dx.doi.org/10.1126/sciadv.aba5136] [PMID: 32596459]
[28]
Behroozi J, Shahbazi S, Bakhtiarizadeh MR, et al. Genome-Wide Characterization of RNA Editing Sites in Primary Gastric Adenocarcinoma through RNA-seq Data Analysis. International Journal of Genomics 2020; 2020: 1-16.
[http://dx.doi.org/10.1155/2020/6493963]
[29]
Permuth JB, Reid B, Earp M, et al. Inherited variants affecting RNA editing may contribute to ovarian cancer susceptibility: results from a large-scale collaboration. Oncotarget 2016; 7(45): 72381-94.
[http://dx.doi.org/10.18632/oncotarget.10546] [PMID: 27911851]
[30]
Zhang F, Lu Y, Yan S, Xing Q, Tian W. SPRINT: an SNP-free toolkit for identifying RNA editing sites. Bioinformatics 2017; 33(22): 3538-48.
[http://dx.doi.org/10.1093/bioinformatics/btx473] [PMID: 29036410]
[31]
Li H, Durbin R. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 2009; 25(14): 1754-60.
[http://dx.doi.org/10.1093/bioinformatics/btp324] [PMID: 19451168]
[32]
Li H, Homer N. A survey of sequence alignment algorithms for next-generation sequencing. Brief Bioinform 2010; 11(5): 473-83.
[http://dx.doi.org/10.1093/bib/bbq015] [PMID: 20460430]
[33]
Li H, Handsaker B, Wysoker A, et al. The Sequence Alignment/Map format and SAMtools. Bioinformatics 2009; 25(16): 2078-9.
[http://dx.doi.org/10.1093/bioinformatics/btp352] [PMID: 19505943]
[34]
Cingolani P, Platts A, Wang L, et al. A program for annotating and predicting the effects of single nucleotide polymorphisms, SnpEff: SNPs in the genome of Drosophila melanogaster strain w1118; iso-2; iso-3. Fly (Austin) 2012; 6(2): 80-92.
[http://dx.doi.org/10.4161/fly.19695] [PMID: 22728672]
[35]
Kim D, Pertea G, Trapnell C, Pimentel H, Kelley R, Salzberg SL. TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions. Genome Biol 2013; 14(4): R36.
[http://dx.doi.org/10.1186/gb-2013-14-4-r36] [PMID: 23618408]
[36]
Trapnell C, Williams BA, Pertea G, et al. Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation. Nat Biotechnol 2010; 28(5): 511-5.
[http://dx.doi.org/10.1038/nbt.1621] [PMID: 20436464]
[37]
Huang W, Sherman BT, Lempicki RA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 2009; 4(1): 44-57.
[http://dx.doi.org/10.1038/nprot.2008.211] [PMID: 19131956]
[38]
Crooks GE, Hon G, Chandonia JM, Brenner SE. WebLogo: a sequence logo generator. Genome Res 2004; 14(6): 1188-90.
[http://dx.doi.org/10.1101/gr.849004] [PMID: 15173120]
[39]
Wang Z, Feng X, Tang Z, Li SC. Genome-Wide Investigation and Functional Analysis of Sus scrofa RNA Editing Sites across Eleven Tissues. Genes (Basel) 2019; 10(5): 327.
[http://dx.doi.org/10.3390/genes10050327] [PMID: 31052161]
[40]
Riffo-Campos ÁL, Riquelme I, Brebi-Mieville P. Tools for sequence-based miRNA target prediction: what to choose? Int J Mol Sci 2016; 17(12): 1987.
[http://dx.doi.org/10.3390/ijms17121987] [PMID: 27941681]
[41]
Krüger J, Rehmsmeier M. RNAhybrid: microRNA target prediction easy, fast and flexible. Nucleic acids research 2006; 34(2): W451-4.
[http://dx.doi.org/10.1093/nar/gkl243]
[42]
Feng X, Wang Z, Li H, Li SC. MIRIA: a webserver for statistical, visual and meta-analysis of RNA editing data in mammals. BMC Bioinformatics 2019; 20(24)(Suppl. 24): 596.
[http://dx.doi.org/10.1186/s12859-019-3242-2] [PMID: 31861975]
[43]
Chen CX, Cho DS, Wang Q, Lai F, Carter KC, Nishikura K. A third member of the RNA-specific adenosine deaminase gene family, ADAR3, contains both single- and double-stranded RNA binding domains. RNA 2000; 6(5): 755-67.
[http://dx.doi.org/10.1017/S1355838200000170] [PMID: 10836796]
[44]
Wang K, Li M, Hakonarson H. ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res 2010; 38(16): e164-4.
[http://dx.doi.org/10.1093/nar/gkq603] [PMID: 20601685]
[45]
Yang CC, Chen YT, Chang YF, et al. ADAR1-mediated 3′ UTR editing and expression control of antiapoptosis genes fine-tunes cellular apoptosis response. Cell Death Dis 2017; 8(5): e2833-3.
[http://dx.doi.org/10.1038/cddis.2017.12] [PMID: 28542129]
[46]
Zhang Y, Huang F, Luo Q, et al. Inhibition of XIAP increases carboplatin sensitivity in ovarian cancer. OncoTargets Ther 2018; 11: 8751-9.
[http://dx.doi.org/10.2147/OTT.S171053] [PMID: 30584333]
[47]
Picardi E, D’Erchia AM, Lo Giudice C, Pesole G. REDIportal: a comprehensive database of A-to-I RNA editing events in humans. Nucleic Acids Res 2017; 45(D1): D750-7.
[http://dx.doi.org/10.1093/nar/gkw767] [PMID: 27587585]
[48]
Rohozinski J, Edwards CL, Anderson ML. Does expression of the retrogene UTP14c in the ovary pre-dispose women to ovarian cancer? Med Hypotheses 2012; 78(4): 446-9.
[http://dx.doi.org/10.1016/j.mehy.2011.12.016] [PMID: 22285623]
[49]
Porath HT, Carmi S, Levanon EY. A genome-wide map of hyper-edited RNA reveals numerous new sites. Nat Commun 2014; 5(1): 4726.
[http://dx.doi.org/10.1038/ncomms5726] [PMID: 25158696]
[50]
Higuchi M, Maas S, Single FN, et al. Point mutation in an AMPA receptor gene rescues lethality in mice deficient in the RNA-editing enzyme ADAR2. Nature 2000; 406(6791): 78-81.
[http://dx.doi.org/10.1038/35017558] [PMID: 10894545]
[51]
Gong J, Liu C, Liu W, et al. LNCediting: a database for functional effects of RNA editing in lncRNAs. Nucleic Acids Res 2017; 45(D1): D79-84.
[http://dx.doi.org/10.1093/nar/gkw835] [PMID: 27651464]
[52]
Ivanov A, Memczak S, Wyler E, et al. Analysis of intron sequences reveals hallmarks of circular RNA biogenesis in animals. Cell Rep 2015; 10(2): 170-7.
[http://dx.doi.org/10.1016/j.celrep.2014.12.019] [PMID: 25558066]

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