Department of Genetics, Washington University School of Medicine, Saint Louis, MO, USA.
Center for Genome Sciences and Systems Biology, Washington University School of Medicine, Saint Louis, MO, USA.
Nat Rev Cancer. 2024 Feb;24(2):123-140. doi: 10.1038/s41568-023-00653-8. Epub 2024 Jan 16.
Transposable elements (TEs) represent almost half of the human genome. Historically deemed 'junk DNA', recent technological advancements have stimulated a wave of research into the functional impact of TEs on gene-regulatory networks in evolution and development, as well as in diseases including cancer. The genetic and epigenetic evolution of cancer involves the exploitation of TEs, whereby TEs contribute directly to cancer-specific gene activities. This Review provides a perspective on the role of TEs in cancer as being a 'double-edged sword', both promoting cancer evolution and representing a vulnerability that could be exploited in cancer therapy. We discuss how TEs affect transcriptome regulation and other cellular processes in cancer. We highlight the potential of TEs as therapeutic targets for cancer. We also summarize technical hurdles in the characterization of TEs with genomic assays. Last, we outline open questions and exciting future research avenues.
转座元件 (TEs) 约占人类基因组的一半。这些元件曾被认为是“垃圾 DNA”，但最近的技术进步激发了一波研究热潮，旨在探索 TEs 在进化和发育过程中对基因调控网络的功能影响，以及在癌症等疾病中的功能影响。癌症的遗传和表观遗传进化涉及到 TEs 的利用，TEs 直接促进了癌症特异性基因的活性。本综述从一个角度探讨了 TEs 在癌症中的作用，认为 TEs 是一把“双刃剑”，既促进了癌症的进化，又代表了一种可以在癌症治疗中加以利用的脆弱性。我们讨论了 TEs 如何影响癌症中的转录组调控和其他细胞过程。我们强调了 TEs 作为癌症治疗靶点的潜力。我们还总结了利用基因组分析技术对 TEs 进行特征描述的技术障碍。最后，我们概述了一些开放性问题和激动人心的未来研究方向。
