LINE-1 retrotransposition and its deregulation in cancers: implications for therapeutic opportunities.
LINE-1 retrotransposition and its deregulation in cancers: implications for therapeutic opportunities.
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DOI：
10.1101/gad.351051.123
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发表时间：
2023-12-26
影响因子：
10.5
通讯作者：
Burns, Kathleen H
中科院分区：
文献类型：
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作者：
Mendez-Dorantes, Carlos;Burns, Kathleen H
在这篇综述中，Mendez-Dorantes 和 Burns 讨论了 LINE-1 逆转录转座的分子机制和基因组后果。 LINE-1 逆转录转座子促进癌症中的基因组不稳定性和免疫激活，作者探索了它们在诊断和治疗干预中的靶向性。长散布元件 1 (LINE-1) 是唯一在人类中具有活性的蛋白质编码转座子。 LINE-1 使用 RNA 中间体通过逆转录转座在基因组中繁殖。这一活动导致 LINE-1 序列占据了我们基因组的大约五分之一。尽管 LINE-1 的大多数拷贝是不可移动的，但~100 个拷贝具有逆转录转座能力。逆转录转座通常受到表观遗传沉默、DNA 修复和其他宿主防御机制的限制。相反，LINE-1 过度表达和逆转录转座是癌症的标志。在这里，我们回顾了 LINE-1 的调控机制以及 LINE-1 如何促进肿瘤的遗传异质性。最后，我们讨论了利用 LINE-1 生物学治疗癌症的治疗策略。
In this review, Mendez-Dorantes and Burns discuss the molecular mechanisms and genomic consequences of LINE-1 retrotransposition. LINE-1 retrotransposons promote genomic instability and immune activation in cancer, and the authors explore their targetability in diagnostic and therapeutic interventions. Long interspersed element 1 (LINE-1) is the only protein-coding transposon that is active in humans. LINE-1 propagates in the genome using RNA intermediates via retrotransposition. This activity has resulted in LINE-1 sequences occupying approximately one-fifth of our genome. Although most copies of LINE-1 are immobile, ∼100 copies are retrotransposition-competent. Retrotransposition is normally limited via epigenetic silencing, DNA repair, and other host defense mechanisms. In contrast, LINE-1 overexpression and retrotransposition are hallmarks of cancers. Here, we review mechanisms of LINE-1 regulation and how LINE-1 may promote genetic heterogeneity in tumors. Finally, we discuss therapeutic strategies to exploit LINE-1 biology in cancers.