Crossing the LINE Toward Genomic Instability: LINE-1 Retrotransposition in Cancer.
Crossing the LINE Toward Genomic Instability: LINE-1 Retrotransposition in Cancer.
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DOI：
10.3389/fchem.2015.00068
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发表时间：
2015
影响因子：
5.5
通讯作者：
Longworth MS
中科院分区：
文献类型：
--
作者：
Kemp JR;Longworth MS
逆转录转座子是位于整个人类基因组中的重复 DNA 序列。逆转录转座子能够自我复制，并将新拷贝转移到新的基因组位置，这一过程称为逆转录转座。虽然人类基因组中的大多数逆转录转座子序列不完整且无法动员，但占人类基因组约 17% 的 LINE-1 逆转录转座子仍然保持活跃。抑制逆转录转座子活性的细胞机制的破坏与非整倍性的产生有关，非整倍性是肿瘤发展的潜在驱动因素。当逆转录转座子插入新的基因组区域时，它们有可能破坏内源基因的编码序列并改变基因表达，这可能会给生物体带来有害后果。此外，增加的 LINE-1 拷贝数为反转录转座子之间发生重组事件提供了更多机会，这可能导致染色体断裂和重排。 LINE-1 活性在各种癌细胞系和从原发性肿瘤切除的患者组织中增加。 LINE-1 活性还与癌症转移增加相关。本综述旨在简要概述 LINE-1 逆转录转座与基因组稳定性丧失之间的联系。我们还将讨论抑制人类细胞逆转录转座的机制及其与癌症的联系。
Retrotransposons are repetitive DNA sequences that are positioned throughout the human genome. Retrotransposons are capable of copying themselves and mobilizing new copies to novel genomic locations in a process called retrotransposition. While most retrotransposon sequences in the human genome are incomplete and incapable of mobilization, the LINE-1 retrotransposon, which comprises~17% of the human genome, remains active. The disruption of cellular mechanisms that suppress retrotransposon activity is linked to the generation of aneuploidy, a potential driver of tumor development. When retrotransposons insert into a novel genomic region, they have the potential to disrupt the coding sequence of endogenous genes and alter gene expression, which can lead to deleterious consequences for the organism. Additionally, increased LINE-1 copy numbers provide more chances for recombination events to occur between retrotransposons, which can lead to chromosomal breaks and rearrangements. LINE-1 activity is increased in various cancer cell lines and in patient tissues resected from primary tumors. LINE-1 activity also correlates with increased cancer metastasis. This review aims to give a brief overview of the connections between LINE-1 retrotransposition and the loss of genome stability. We will also discuss the mechanisms that repress retrotransposition in human cells and their links to cancer.