综述

癌症相关microRNA与靶基因的生物信息学分析

展开
  • 1. 南京师范大学泰州学院化学与生物工程学院,泰州 225300;
    2. 第三军医大学大坪医院健康管理科,重庆 400042;
    3. 南京师范大学生命科学学院,南京 210046
周学,博士,讲师,专业方向:非编码RNA。E-mail:zhousuxia88@126.com

收稿日期: 2015-03-22

  修回日期: 2015-07-06

  网络出版日期: 2015-09-20

基金资助

南京师范大学泰州学院青年项目(编号:Q201206)资助

Bioinformatic analysis of cancer-related microRNAs and their target genes

Expand
  • 1. School of Chemistry and Biological Engineering, Nanjing Normal University Taizhou College, Taizhou 225300, China;
    2. Health Management Department of Daping Hospital, Third Military Medical University, Chongqing 400042,China;
    3. College of Life Science, Nanjing Normal University, Nanjing 210046, China

Received date: 2015-03-22

  Revised date: 2015-07-06

  Online published: 2015-09-20

摘要

MicroRNAs(miRNAs)是一类长度约为22nt的内源性非编码RNA,通过与靶基因转录本互补结合调控基因的表达。近年来,研究发现miRNA与癌症发生密切相关,miRNA可以直接充当癌基因或者抑癌基因而影响肿瘤的发生和生长。为更进一步揭示癌症相关miRNA的特征及靶基因的功能,文章通过数据库搜索及文献检索,在人类基因组中发现了475个癌症相关miRNA,系统地比较了癌症相关miRNA与非癌症miRNA以及基因内和基因间区癌症相关miRNA在保守性、SNP位点分布、癌谱及转录调控等特性。研究发现,癌症相关miRNA比非癌症miRNA保守性要强,发生SNP概率比较低,同时发现miRNA所涉及癌症数目与保守性成正相关。基因组定位分析发现,癌症相关miRNA比非癌症miRNA更倾向于成簇存在。进一步对宿主基因、癌症相关miRNA及作用的靶基因与癌症发生进行关联分析,发现一些非癌症miRNA的宿主基因倾向于被癌症miRNA作用。本研究结果为深入理解miRNA与癌症之间的关系,以及进一步为miRNA作为癌症诊断指示物提供理论依据。

本文引用格式

周学, 杜宜兰, 金萍, 马飞 . 癌症相关microRNA与靶基因的生物信息学分析[J]. 遗传, 2015 , 37(9) : 855 -864 . DOI: 10.16288/j.yczz.14-439

Abstract

MicroRNAs (miRNAs) are a class of ~22 nucleotide endogenous noncoding RNAs which regulate gene expression by targeting complementary transcripts. Recent studies have found that miRNAs are closely related to tumorigenesis and can act as oncogenes or tumor suppressor genes to influence the occurrence and development of tumor. To further reveal characteristics of cancer-related miRNAs and the functions of miRNA targets, we obtained 475 miRNAs involved in cancer through database searching and information retrieval. We systematically analyzed and compared the features including conservation, SNP distribution, cancer spectrum width, and transcriptional regulation between cancer and non-cancer related miRNAs as well as between intergenic and intragenic miRNAs. Our results showed that cancer-related miRNAs have higher conservation and lower SNP frequency compared to non-cancer-related miRNAs, and the cancer spectrum of one miRNA is positively correlated with its conservation. Genome analysis showed that cancer-related miRNAs tend to present as clusters compared with non-cancer-related miRNAs. Further association analysis between cancer progression and host genes, cancer-related miRNAs or target genes found that the host genes of some non-cancer related miRNAs tend to be targeted by cancer-related miRNAs. This study provides theoretical basis for further understanding the relationship between miRNA and cancer progression as well as the miRNA-based cancer diagnosis.

参考文献

[1] Lee Y, Kim M, Han JJ, Yeom KH, Lee S, Baek SH, Kim VN. MicroRNA genes are transcribed by RNA polymerase II. EMBO J , 2004, 23(20): 4051-4060.
[2] Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14 . Cell , 1993, 75(5): 843-854.
[3] Wightman B, Ha I, Ruvkun G. Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans . Cell , 1993, 75(5): 855-862.
[4] Ambros V, Bartel B, Bartel DP, Burge CB, Carrington JC, Chen XM, Dreyfuss G, Eddy SR, Griffiths-Jones S, Marshall M, Matzke M, Ruvkun G, Tuschl T. A uniform system for microRNA annotation. RNA , 2003, 9(3): 277-279.
[5] Bushati N, Cohen SM. microRNA functions. Annu Rev Cell Dev Biol , 2007, 23: 175-205.
[6] Sun BK, Tsao H. Small RNAs in development and disease. J Am Acad Dermatol , 2008, 59(5): 725-737.
[7] Brase JC, Wuttig D, Kuner R, Sültmann H. Serum microRNAs as non-invasive biomarkers for cancer. Mol Cancer , 2010, 9(1): 306.
[8] Cortez MA, Calin GA. MicroRNA identification in plasma and serum: a new tool to diagnose and monitor diseases. Expert Opin Biol Ther , 2009, 9(6): 703-711.
[9] Kozomara A, Griffiths-Jones S. miRBase: integrating microRNA annotation and deep-sequencing data. Nucleic Acids Res , 2011, 39(Database issue): D152-D157.
[10] Griffiths-Jones S, Saini HK, van Dongen S, Enright AJ. miRBase: tools for microRNA genomics. Nucleic Acids Res , 2008, 36(Database issue): D154-D158.
[11] Monteys AM, Spengler RM, Wan J, Tecedor L, Lennox KA, Xing Y, Davidson BL. Structure and activity of putative intronic miRNA promoters. RNA , 2010, 16(3): 495-505.
[12] Altuvia Y, Landgraf P, Lithwick G, Elefant N, Pfeffer S, Aravin A, Brownstein MJ, Tuschl T, Margalit H. Clustering and conservation patterns of human microRNAs. Nucleic Acids Res , 2005, 33(8): 2697-2706.
[13] Yu J, Wang F, Yang GH, Wang FL, Ma YN, Du ZW, Zhang JW. Human microRNA clusters: genomic organization and expression profile in leukemia cell lines. Biochem Biophys Res Commun , 2006, 349(1): 59-68.
[14] Kasinski AL, Slack FJ. Epigenetics and genetics. MicroRNAs en route to the clinic: progress in validating and targeting microRNAs for cancer therapy. Nat Rev Cancer , 2011, 11(12): 849-864.
[15] Calin GA, Sevignani C, Dumitru CD, Hyslop T, Noch E, Yendamuri S, Shimizu M, Rattan S, Bullrich F, Negrini M, Croce CM. Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci USA , 2004, 101(9): 2999-3004.
[16] Zhang BH, Pan XP, Cobb GP, Anderson TA. microRNAs as oncogenes and tumor suppressors. Dev Biol , 2007, 302(1): 1-12.
[17] Volinia S, Calin GA, Liu CG, Ambs S, Cimmino A, Petrocca F, Visone R, Iorio M, Roldo C, Ferracin M, Prueitt RL, Yanaihara N, Lanza G, Scarpa A, Vecchione A, Negrini M, Harris CC, Croce CM. A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci USA , 2006, 103(7): 2257-2261.
[18] Lee YS, Kim HK, Chung S, Kim KS, Dutta A. Depletion of human micro-RNA miR-125b reveals that it is critical for the proliferation of differentiated cells but not for the down-regulation of putative targets during differentiation. J Biol Chem , 2005, 280(17): 16635-16641.
[19] Roldo C, Missiaglia E, Hagan JP, Falconi M, Capelli P, Bersani S, Calin GA, Volinia S, Liu CG, Scarpa A, Croce CM. MicroRNA expression abnormalities in pancreatic endocrine and acinar tumors are associated with distinctive pathologic features and clinical behavior. J Clin Oncol , 2006, 24(29): 4677-4684.
[20] Chang TC, Wentzel EA, Kent OA, Ramachandran K, Mullendore M, Lee KH, Feldmann G, Yamakuchi M, Ferlito M, Lowenstein CJ, Arking DE, Beer MA, Maitra A, Mendell JT. Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis. Mol Cell , 2007, 26(5): 745-752.
[21] Lodyg
文章导航

/