[1]陈梦竹,王秀杰,夏立新.肺腺癌和肺鳞癌中mRNA可变剪接特征的比较[J].深圳大学学报理工版,2017,34(1):33-45.[doi:10.3724/SP.J.1249.2017.01033]
 Chen Mengzhu,Wang Xiujie,and Xia Lixin.Comparison of alternative splicing in lung adenocarcinoma and lung squamous carcinoma[J].Journal of Shenzhen University Science and Engineering,2017,34(1):33-45.[doi:10.3724/SP.J.1249.2017.01033]
点击复制

肺腺癌和肺鳞癌中mRNA可变剪接特征的比较()
分享到:

《深圳大学学报理工版》[ISSN:1000-2618/CN:44-1401/N]

卷:
第34卷
期数:
2017年第1期
页码:
33-45
栏目:
生物工程
出版日期:
2017-01-09

文章信息/Info

Title:
Comparison of alternative splicing in lung adenocarcinoma and lung squamous carcinoma
文章编号:
201701006
作者:
陈梦竹1王秀杰2夏立新1
1) 深圳大学医学部,呼吸疾病国家重点实验室深圳大学变态反应分室,广东深圳518060
2) 中国科学院遗传与发育生物学研究所,北京100101
Author(s):
Chen Mengzhu1 Wang Xiujie2 and Xia Lixin1
1) State Key Laboratory of Respiratory Disease for Allergy at Shenzhen University, Health Science Center, Shenzhen University, Shenzhen 518060, Guangdong Province, P.R.China
2) Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, P.R.China
关键词:
生物信息学肺腺癌肺鳞癌可变剪接外显子跳跃可变起始外显子
Keywords:
bioinformatics lung adenocarcinoma (LUAD) lung squamous carcinoma (LUSC) alternative splicing (AS) skipping exon (SE) alternative first exon (AF)
分类号:
R 734.2;Q 811.4
DOI:
10.3724/SP.J.1249.2017.01033
文献标志码:
A
摘要:
利用SUPPA(a super-fast pipeline for alternative splicing)软件分析癌症基因组数据库癌基因组图谱中肺腺癌和肺鳞癌样本的RNA-Seq数据,发现在鉴定的7种主要可变剪接转录本中外显子跳跃转录本发生频率最高.通过癌组织与癌旁组织的比较,系统地鉴定了肺腺癌和肺鳞癌中差异表达的可变剪接转录本,发现约60%的差异可变剪接转录本是两种肺癌亚型所共有的.功能富集分析表明,癌组织特异的可变剪接转录本主要富集在细胞周期调控、脱氧核糖核酸代谢和核糖核酸代谢等生物过程中,而癌旁组织特异的可变剪接转录本则主要富集在囊泡介导转运、多肽转运和脂质转运等生物过程中.通过肺癌驱动基因可变剪接转录本的比较分析,鉴定了两种肺癌亚型共有或特有的可能具有癌驱动功能的可变剪接转录本.
Abstract:
Lung cancer is a common disease with high morbidity and mortality. Studies have shown that alternative splicing (AS) is closely associated with lung carcinogenesis, but the difference of alternative splicing between lung adenocarcinoma (LUAD) and lung squamous carcinoma (LUSC) remains unclear. Here, we analyze the RNA-Seq data of LUAD and LUSC from TCGA using SUPPA software, and find that skipping exon (SE) is the most frequently occurred AS transcript among seven main AS transcripts identified. By comparing tumor tissues with normal ones, we systematically identify differentially expressed AS transcripts in both LUAD and LUSC, of which around 60% are identical between these two subtypes. Functional analysis reveals that tumor-specific AS transcripts are mainly enriched among genes associated with cell cycle regulation, deoxyribonucleic acid metabolism and RNA metabolism, whereas normal-specific AS transcripts are enriched among genes mainly involved in vesicle-mediated transport, peptide transport and lipid transport. By comparing AS transcripts of cancer-driven genes between LUAD and LUSC, we identify some common and subtype-specific AS transcripts with cancer-driven potentiality.

参考文献/References:

[1] Siegel R L, Miller K D, Jemal A. Cancer statistics, 2015[J]. CA: A Cancer Journal for Clinicians, 2015, 65(1): 5-29.
[2] Chen Wanqing, Zheng Rongshou, Baade P D, et al. Cancer statistics in China, 2015[J]. CA: A Cancer Journal for Clinicians, 2016, 66(2): 115-132.
[3] Chang J T H, Lee Y M, Huang R S. The impact of the Cancer Genome Atlas on lung cancer[J]. Translational Research, 2015, 166(6): 568-585.
[4] Subramanian J, Govindan R. Lung cancer in never smokers: a review[J]. Journal of Clinical Oncology, 2007, 25(5): 561-570.
[5] Hammerman P S, Lawrence M S, Voet D, et al. Comprehensive genomic characterization of squamous cell lung cancers[J]. Nature, 2012, 489(7417): 519-525.
[6] Collisson E A, Campbell J D, Brooks A N, et al. Comprehensive molecular profiling of lung adenocarcinoma[J]. Nature, 2014, 511(7511): 543-550.
[7] Paez J G, Jnne P A, Lee J C, et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy[J]. Science, 2004, 304(5676): 1497-1500.
[8] Antonicelli A, Cafarotti S, Indini A, et al. EGFR-targeted therapy for non-small cell lung cancer: focus on EGFR oncogenic mutation[J]. International Journal of Medical Sciences, 2013, 10(3): 320-330.
[9] Rekhtman N, Paik P K, Arcila M E, et al. Clarifying the spectrum of driver oncogene mutations in biomarker-verified squamous carcinoma of lung: lack of EGFR/KRAS and presence of PIK3CA/AKT1 mutations[J]. Clinical Cancer Research, 2012, 18(4): 1167-1176.
[10] Pan Qun, Shai O, Lee L J, et al. Deep surveying of alternative splicing complexity in the human transcriptome by high-throughput sequencing[J]. Nature Genetics, 2008, 40(12): 1413-1415.
[11] Chen Mo, Manley J L. Mechanisms of alternative splicing regulation: insights from molecular and genomics approaches[J]. Nature Reviews Molecular Cell Biology, 2009, 10(11): 741-754.
[12] Wahl M C, Will C L, Lührmann R. The spliceosome: design principles of a dynamic RNP machine[J]. Cell, 2009, 136(4): 701-718.
[13] Venables J P, Klinck R, Koh C, et al. Cancer-associated regulation of alternative splicing[J]. Nature Structural & Molecular Biology, 2009, 16(6): 670-676.
[14] Chen J, Weiss W A. Alternative splicing in cancer: implications for biology and therapy[J]. Oncogene, 2015, 34(1): 1-14.
[15] Takehara T, Liu Xiaolong, Fujimoto J, et al. Expression and role of Bcl-xL in human hepatocellular carcinomas[J]. Hepatology, 2001, 34(1): 55-61.
[16] Alamancos GP, Pagès A, Trincado JL, et al. Leveraging transcript quantification for fast computation of alternative splicing profiles[J]. RNA, 2015, 21(9): 1521-1531.
[17] Huang Dawei, Sherman B T, Lempicki R A. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources[J]. Nature Protocols, 2009, 4(1): 44-57.
[18] Supek F, Bonjak M, kunca N, et al. REVIGO summarizes and visualizes long lists of gene ontology terms[J]. PLoS One, 2011, 6(7): e21800.
[19] Finn R D, Coggill P, Eberhardt R Y, et al. The Pfam protein families database: towards a more sustainable future[J]. Nucleic Acids Research, 2016, 44(D1): D279-D285.
[20] Wamg Z N, Lo H S, Yang H, et al. Computational analysis and experimental validation of tumor-associated alternative RNA splicing in human cancer[J]. Cancer Research, 2003, 63(3): 655-657.
[21] Pio R, Blanco D, Pajares M J, et al. Development of a novel splice array platform and its application in the identification of alternative splice variants in lung cancer[J]. BMC Genomics, 2010, 11: 352.
[22] Planque C, Choi Y H, Guyetant S, et al. Alternative splicing variant of kallikrein-related peptidase 8 as an independent predictor of unfavorable prognosis in lung cancer[J]. Clinical Chemistry, 2010, 56(6): 987-997.
[23] Fan Y C, Min L, Chen H, et al. Alternative splicing isoform of T cell factor 4 K suppresses the proliferation and metastasis of non-small cell lung cancer cells[J]. Genetics and Molecular Research : GMR, 2015, 14(4): 14009-14018.
[24] Misquitta-Ali CM, Cheng E, O’Hanlon D, et al. Global profiling and molecular characterization of alternative splicing events misregulated in lung cancer[J]. Molecular and Cellular Biology, 2011, 31(1): 138-150.
[25] Pelosi G, Schianchi E, Dell’orto P, et al. Detecting cell-free circulating hTERT mRNA in the plasma may identify a subset of nonsmall cell lung cancer patients[J]. Laboratory Investigation, 2006, 448(1): 7-15.
[26] Fujiwara M, Kamma H, Wu W, et al. Expression and alternative splicing pattern of human telomerase reverse transcriptase in human lung cancer cells[J]. International Journal of Oncology, 2004, 24(4): 925-930.

相似文献/References:

[1]夏立新,闫浩,汤慕瑾,等.花生过敏原Ara h2与Ara h6的生物信息学比较研究[J].深圳大学学报理工版,2010,27(2):241.
 XIA Li-xin,YAN Hao,TANG Mu-jin,et al.Bioinformatics comparison of peanut allergen Ara h2 and Ara h6[J].Journal of Shenzhen University Science and Engineering,2010,27(1):241.
[2]唐玉林,曹雁,欧忠华,等.非生物胁迫因子对大豆Sali3-2基因的调控作用[J].深圳大学学报理工版,2012,29(No.1(001-094)):73.[doi:10.3724/SP.J.1249.2012.01073]
 TANG Yu-lin,CAO Yan,OU Zhong-hua,et al.Regulatable gene expression controlled by the promoter of Sali3-2 under different abiotic stresses[J].Journal of Shenzhen University Science and Engineering,2012,29(1):73.[doi:10.3724/SP.J.1249.2012.01073]
[3]毕得,肖华军,周翠红,等.心肺细胞缺氧效应生物信息学分析[J].深圳大学学报理工版,2012,29(No.6(471-580)):541.[doi:10.3724/SP.J.1249.2012.06541]
 BI De,XIAO Hua-jun,ZHOU Cui-hong,et al.Bioinformatic analysis of ?cardiac and pulmonary hypoxia[J].Journal of Shenzhen University Science and Engineering,2012,29(1):541.[doi:10.3724/SP.J.1249.2012.06541]
[4]娄素琳,朱秀兰,曾志勇,等.盐藻microRNA高通量测序和生物信息学分析[J].深圳大学学报理工版,2018,35(4):331.[doi:10.3724/SP.J.1249.2018.04331]
 LOU Sulin,ZHU Xiulan,ZENG Zhiyong,et al.Bioinformatics analysis of Dunaliella microRNAs by high-throughput sequencing[J].Journal of Shenzhen University Science and Engineering,2018,35(1):331.[doi:10.3724/SP.J.1249.2018.04331]
[5]张尉欣,刘阳,刘 帅,等.镉胁迫下菜心的转录组分析[J].深圳大学学报理工版,2018,35(5):543.[doi:10.3724/SP.J.1249.2018.05543]
 ZHANG Weixin,LIU Yang,LIU Shuai,et al.Transcriptome analysis of Brassica rapa ssp. chinensis var. parachinensis under cadmium stress[J].Journal of Shenzhen University Science and Engineering,2018,35(1):543.[doi:10.3724/SP.J.1249.2018.05543]
[6]钟姗,等.食管鳞癌中3个新miRNA的分子功能预测[J].深圳大学学报理工版,2019,36(4):347.[doi:10.3724/SP.J.1249.2019.04347]
 ZHONG Shan,WANG Yun,et al.The prediction of molecular functions for three novel miRNAs in esophageal squamous cell carcinoma[J].Journal of Shenzhen University Science and Engineering,2019,36(1):347.[doi:10.3724/SP.J.1249.2019.04347]
[7]须周恒,朱营利,孙孟菲,等.小鼠纹状体与视网膜的比较转录组学分析[J].深圳大学学报理工版,2020,37(1):17.[doi:10.3724/SP.J.1249.2020.01017]
 XU Zhouheng,ZHU Yingli,SUN Mengfei,et al.Comparative transcriptomic analysis of mouse striatum and retina[J].Journal of Shenzhen University Science and Engineering,2020,37(1):17.[doi:10.3724/SP.J.1249.2020.01017]

备注/Memo

备注/Memo:
Received:2016-06-18;Revised:2016-11-14;Accepted:2016-11-20
Foundation:National High-Tech Research and Development Program (2012AA020409); Shenzhen Science and Technology Basic Research Foundation(JCYJ20150525092941055)
Corresponding author:Professor Wang Xiujie. E-mail: xjwang@genetics.ac.cn; Professor Xia Lixin. E-mail:xialixin@126.com
Citation:Chen Mengzhu, Wang Xiujie, Xia Lixin. Comparison of alternative splicing in lung adenocarcinoma and lung squamous carcinoma[J]. Journal of Shenzhen University Science and Engineering, 2017, 34(1): 33-45.(in Chinese)
基金项目:国家高技术研究发展计划资助项目(2012AA020409);深圳市知识创新计划基础研究资助项目(JCYJ20150525092941055)
作者简介:陈梦竹(1982—),女,深圳大学博士后研究人员.研究方向:生物信息学.E-mail:mzchen@szu.edu.cn
引文:陈梦竹,王秀杰,夏立新.肺腺癌和肺鳞癌中mRNA可变剪接特征的比较[J]. 深圳大学学报理工版,2017,34(1):33-45.
更新日期/Last Update: 2016-12-30