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逆转录转座子LINE-1与肿瘤的发生和发展

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  • 1. 中国医学科学院&北京协和医学院 医药生物技术研究所免疫生物学室,北京 100050;
    2. 中国医学科学院&北京协和医学院 北京协和医院妇产科,北京 100730
刘茜,硕士研究生,专业方向:MOV10抑制LINE-1分子机制的研究。E-mail: shine_lqian@163.com

收稿日期: 2015-11-16

  修回日期: 2015-12-02

  网络出版日期: 2016-01-05

基金资助

国家自然科学基金项目(编号:31270210)资助[Supported by the National Natural Science Foundation of China (No.31270210)]

The connection between LINE-1 retrotransposition and human tumorigenesis

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  • 1. Department of Immunology, Institute of Medicinal Biotechnology, Chinese academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China;
    2. Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China

Received date: 2015-11-16

  Revised date: 2015-12-02

  Online published: 2016-01-05

摘要

LINE-1是现今人体内存在的唯一具有自主转座活性的转座子,约有500 000个拷贝,占人类基因组总量的17%。LINE-1是通过转录和逆转录在内的转座过程产生新的DNA拷贝,并使新产生的DNA拷贝插入基因组的不同位置。LINE-1转座会影响基因组中其他基因的表达或调控,因而会对基因组的稳定性产生影响,从而导致基因疾病或肿瘤的发生。本文总结了近年来国际上对LINE-1转座与肿瘤的发生和发展之间关系的研究进展,为肿瘤的治疗和机制研究提供一些线索。

本文引用格式

刘茜,王瑾晖,李晓宇,岑山 . 逆转录转座子LINE-1与肿瘤的发生和发展[J]. 遗传, 2016 , 38(2) : 93 -102 . DOI: 10.16288/j.yczz.15-470

Abstract

LINE-1 is the only currently known active autonomous transposon in humans with an estimated 500 000 copies representing 17% of the human genome. LINE-1 propagates itself through a process called retrotransposition, which includes transcription and reverstranscription, to produce new DNA copies. The new produced DNA copies can integrate into new genomic loci. The insertion of LINE-1 is able to cause genetic instability by affecting the expression or regulation of the nearby genes, thus causing dozens of genetic diseases or tumors. In this review, we summarize the recent research progress on the connection between LINE-1 retrotransposition and human tumorigenesis, which might shed light on the biology mechanisms and treatment of the tumorigenesis.

参考文献

[1] Unwin N. The Croonian Lecture 2000. Nicotinic acetylcholine receptor and the structural basis of fast synaptic transmission. Philos Trans R Soc Lond B Biol Sci , 2000, 355(1404): 1813-1829.
[2] McClintock B. The origin and behavior of mutable loci in maize. Proc Natl Acad Sci USA , 1950, 36(6): 344-355.
[3] Goodier JL, Kazazian HH Jr. Retrotransposons revisited: the restraint and rehabilitation of parasites. Cell , 2008, 135(1): 23-35.
[4] Bao WD, Kojima KK, Kohany O. Repbase Update, a database of repetitive elements in eukaryotic genomes. Mob DNA , 2015, 6: 11.
[5] Blikstad V, Benachenhou F, Sperber GO, Blomberg J. Endogenous retroviruses-evolution of human endogenous retroviral sequences: a conceptual account. Cell Mol Life Sci , 2008, 65(21): 3348-3365.
[6] Belancio VP, Hedges DJ, Deininger P. Mammalian non-LTR retrotransposons: for better or worse, in sickness and in health. Genome Res , 2008, 18(3): 343-358.
[7] Beck CR, Garcia-Perez JL, Badge RM, Moran JV. LINE-1 elements in structural variation and disease. Annu Rev Genomics Hum Genet , 2011, 12: 187-215.
[8] Swergold GD. Identification, characterization, and cell specificity of a human LINE-1 promoter. Mol Cell Biol , 1990, 10(12): 6718-6729.
[9] Severynse DM, Hutchison CA 3rd, Edgell MH. Identification of transcriptional regulatory activity within the 5' A-type monomer sequence of the mouse LINE-1 retroposon. Mamm Genome , 1992, 2(1): 41-50.
[10] Feng QH, Moran JV, Kazazian HH Jr, Boeke JD. Human L1 retrotransposon encodes a conserved endonuclease required for retrotransposition. Cell , 1996, 87(5): 905-916.
[11] Martin SL, Li JF, Epperson LE, Lieberman B. Functional reverse transcriptases encoded by A-type mouse LINE-1: defining the minimal domain by deletion analysis. Gene , 1998, 215(1): 69-75.
[12] Moran JV, Holmes SE, Naas TP, DeBerardinis RJ, Boeke JD, Kazazian HH Jr. High frequency retrotransposition in cultured mammalian cells. Cell , 1996, 87(5): 917-927.
[13] Belgnaoui SM, Gosden RG, Semmes OJ, Haoudi A. Human LINE-1 retrotransposon induces DNA damage and apoptosis in cancer cells. Cancer Cell Int , 2006, 6: 13.
[14] Babushok DV, Kazazian HH Jr. Progress in understanding the biology of the human mutagen LINE-1. Hum Mutat , 2007, 28(6): 527-539.
[15] Farkash EA, Kao GD, Horman SR, Luning Prak ET. Gamma radiation increases endonuclease-dependent L1 retrotransposition in a cultured cell assay. Nucleic Acids Res , 2006, 34(4): 1196-1204.
[16] Gasior SL, Wakeman TP, Xu B, Deininger PL. The human LINE-1 retrotransposon creates DNA double-strand breaks. J Mol Bio , 2006, 357(5): 1383-1393.
[17] Denli AM, Narvaiza I, Kerman BE, Pena M, Benner C, Marchetto MCN, Diedrich JK, Aslanian A, Ma J, Moresco JJ, Moore L, Hunter T, Saghatelian A, Gage FH. Primate-specific ORF0 contributes to retrotransposon-mediated diversity. Cell , 2015, 163(3): 583-593.
[18] Yoder JA, Walsh CP, Bestor TH. Cytosine methylation and the ecology of intragenomic parasites. Trends Genet , 1997, 13(8): 335-340.
[19] Bourc'his D, Bestor TH. Meiotic catastrophe and retrotransposon reactivation in male germ cells lacking Dnmt3L. Nature , 2004, 431(7004):96-99.
[20] Kato Y, Kaneda M, Hata K, Kumaki K, Hisano M, Kohara Y, Okano M, Li E, Nozaki M, Sasaki H. Role of the Dnmt3 family in de novo methylation of imprinted and repetitive sequences during male germ cell development in the mouse. Hum Mol Genet , 2007, 16(19): 2272-2280.
[21] Branciforte D, Martin SL. Developmental and cell type specificity of LINE-1 expression in mouse testis: implications for transposition. Mol Cell Biol , 1994, 14(4): 2584-2592.
[22] Kano H, Godoy I, Courtney C, Vetter MR, Gerton GL, Ostertag EM, Kazazian HH Jr. L1 retrotransposition occurs mainly in embryogenesis and creates somatic mosaicism. Genes Dev , 2009, 23(11): 1303-1312.
[23] Garcia-Perez JL, Marchetto MCN, Muotri AR, Coufal NG, Gage FH, O'Shea KS, Moran
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