Towards Targeting Transposable Elements for Cancer Therapy

Overview

Journal Nat Rev Cancer

Specialty Oncology

Date 2024 Jan 16

PMID 38228901

Authors

Yonghao Liang

Xuan Qu

Nakul M Shah

Ting Wang

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Long-read RNA sequencing enables full-length chimeric transcript annotation of transposable elements in lung adenocarcinoma.

Li Y, Liu Y, Xie Y, Wang Y, Wang J, Wang H BMC Cancer. 2025; 25(1):482.

PMID: 40089719 DOI: 10.1186/s12885-025-13888-5.

The impact of retrotransposons on zygotic genome activation and the chromatin landscape of early embryos.

Solberg T, Kobayashi-Ishihara M, Siomi H Ann N Y Acad Sci. 2024; 1542(1):11-24.

PMID: 39576233 PMC: 11668504. DOI: 10.1111/nyas.15260.

Long-read RNA sequencing: A transformative technology for exploring transcriptome complexity in human diseases.

Ament I, DeBruyne N, Wang F, Lin L Mol Ther. 2024; 33(3):883-894.

PMID: 39563027 PMC: 11897757. DOI: 10.1016/j.ymthe.2024.11.025.

Sensing of endogenous retroviruses-derived RNA by ZBP1 triggers PANoptosis in DNA damage and contributes to toxic side effects of chemotherapy.

Wang F, Li K, Wang W, Hui J, He J, Cai J Cell Death Dis. 2024; 15(10):779.

PMID: 39465258 PMC: 11514216. DOI: 10.1038/s41419-024-07175-7.

Evolution of Repetitive Elements, Their Roles in Homeostasis and Human Disease, and Potential Therapeutic Applications.

Snowbarger J, Koganti P, Spruck C Biomolecules. 2024; 14(10).

PMID: 39456183 PMC: 11506328. DOI: 10.3390/biom14101250.

References

Hanahan D . Hallmarks of Cancer: New Dimensions. Cancer Discov. 2022; 12(1):31-46. DOI: 10.1158/2159-8290.CD-21-1059. View

Hanahan D, Weinberg R . Hallmarks of cancer: the next generation. Cell. 2011; 144(5):646-74. DOI: 10.1016/j.cell.2011.02.013. View

Black J, McGranahan N . Genetic and non-genetic clonal diversity in cancer evolution. Nat Rev Cancer. 2021; 21(6):379-392. DOI: 10.1038/s41568-021-00336-2. View

Davila M, Brentjens R . CAR T cell therapy: looking back and looking forward. Nat Cancer. 2022; 3(12):1418-1419. DOI: 10.1038/s43018-022-00484-w. View

Cordaux R, Batzer M . The impact of retrotransposons on human genome evolution. Nat Rev Genet. 2009; 10(10):691-703. PMC: 2884099. DOI: 10.1038/nrg2640. View

Feschotte C, Pritham E . DNA transposons and the evolution of eukaryotic genomes. Annu Rev Genet. 2007; 41:331-68. PMC: 2167627. DOI: 10.1146/annurev.genet.40.110405.090448. View

Hartl D, Lozovskaya E, Lawrence J . Nonautonomous transposable elements in prokaryotes and eukaryotes. Genetica. 1992; 86(1-3):47-53. DOI: 10.1007/BF00133710. View

Sun C, Feschotte C, Wu Z, Lockridge Mueller R . DNA transposons have colonized the genome of the giant virus Pandoravirus salinus. BMC Biol. 2015; 13:38. PMC: 4495683. DOI: 10.1186/s12915-015-0145-1. View

Wicker T, Sabot F, Hua-Van A, Bennetzen J, Capy P, Chalhoub B . A unified classification system for eukaryotic transposable elements. Nat Rev Genet. 2007; 8(12):973-82. DOI: 10.1038/nrg2165. View

10.

Kazazian Jr H, Moran J . Mobile DNA in Health and Disease. N Engl J Med. 2017; 377(4):361-370. PMC: 5980640. DOI: 10.1056/NEJMra1510092. View

11.

Burns K . Transposable elements in cancer. Nat Rev Cancer. 2017; 17(7):415-424. DOI: 10.1038/nrc.2017.35. View

12.

Modzelewski A, Gan Chong J, Wang T, He L . Mammalian genome innovation through transposon domestication. Nat Cell Biol. 2022; 24(9):1332-1340. PMC: 9729749. DOI: 10.1038/s41556-022-00970-4. View

13.

Fueyo R, Judd J, Feschotte C, Wysocka J . Roles of transposable elements in the regulation of mammalian transcription. Nat Rev Mol Cell Biol. 2022; 23(7):481-497. PMC: 10470143. DOI: 10.1038/s41580-022-00457-y. View

14.

Lawson H, Liang Y, Wang T . Transposable elements in mammalian chromatin organization. Nat Rev Genet. 2023; 24(10):712-723. DOI: 10.1038/s41576-023-00609-6. View

15.

Hancks D, Kazazian Jr H . Roles for retrotransposon insertions in human disease. Mob DNA. 2016; 7:9. PMC: 4859970. DOI: 10.1186/s13100-016-0065-9. View

16.

Payer L, Steranka J, Yang W, Kryatova M, Medabalimi S, Ardeljan D . Structural variants caused by insertions are associated with risks for many human diseases. Proc Natl Acad Sci U S A. 2017; 114(20):E3984-E3992. PMC: 5441760. DOI: 10.1073/pnas.1704117114. View

17.

Kazazian Jr H, Wong C, Youssoufian H, Scott A, Phillips D, Antonarakis S . Haemophilia A resulting from de novo insertion of L1 sequences represents a novel mechanism for mutation in man. Nature. 1988; 332(6160):164-6. DOI: 10.1038/332164a0. View

18.

Miki Y, Nishisho I, Horii A, Miyoshi Y, Utsunomiya J, Kinzler K . Disruption of the APC gene by a retrotransposal insertion of L1 sequence in a colon cancer. Cancer Res. 1992; 52(3):643-5. View

19.

Scott E, Gardner E, Masood A, Chuang N, Vertino P, Devine S . A hot L1 retrotransposon evades somatic repression and initiates human colorectal cancer. Genome Res. 2016; 26(6):745-55. PMC: 4889970. DOI: 10.1101/gr.201814.115. View

20.

Cajuso T, Sulo P, Tanskanen T, Katainen R, Taira A, Hanninen U . Retrotransposon insertions can initiate colorectal cancer and are associated with poor survival. Nat Commun. 2019; 10(1):4022. PMC: 6731219. DOI: 10.1038/s41467-019-11770-0. View