LINE-1 基因逆转及其在癌症中的失调：对治疗机会的影响

IF 7.5 1区生物学 Q1 CELL BIOLOGY

Genes & development Pub Date : 2023-12-13 DOI:10.1101/gad.351051.123

Carlos Mendez-Dorantes, Kathleen H. Burns

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引用次数: 0

摘要

长穿插元件 1（LINE-1）是唯一在人类中活跃的蛋白质编码转座子。LINE-1 利用 RNA 中间体通过逆转录在基因组中传播。这种活性导致 LINE-1 序列占据了人类基因组的大约五分之一。虽然 LINE-1 的大多数拷贝是固定的，但有 100 个拷贝具有逆转录能力。逆转录通常通过表观遗传沉默、DNA修复和其他宿主防御机制加以限制。相反，LINE-1过表达和逆转录是癌症的特征。在此，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，我们将讨论在癌症中利用LINE-1生物学特性的治疗策略。

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LINE-1 retrotransposition and its deregulation in cancers: implications for therapeutic opportunities

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.

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来源期刊

Genes & development 生物-发育生物学

CiteScore

17.50

自引率

1.90%

发文量

审稿时长

3-6 weeks

期刊介绍： Genes & Development is a research journal published in association with The Genetics Society. It publishes high-quality research papers in the areas of molecular biology, molecular genetics, and related fields. The journal features various research formats including Research papers, short Research Communications, and Resource/Methodology papers. Genes & Development has gained recognition and is considered as one of the Top Five Research Journals in the field of Molecular Biology and Genetics. It has an impressive Impact Factor of 12.89. The journal is ranked #2 among Developmental Biology research journals, #5 in Genetics and Heredity, and is among the Top 20 in Cell Biology (according to ISI Journal Citation Reports®, 2021).