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RNA-driven JAZF1-SUZ12 gene fusion in human endometrial stromal cells
Oncogenic fusion genes as the result of chromosomal rearrangements are important for understanding genome instability in cancer cells and developing useful cancer therapies. To date, the mechanisms that create such oncogenic fusion genes are poorly understood. Previously we reported an unappreciated...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8722726/ https://www.ncbi.nlm.nih.gov/pubmed/34928964 http://dx.doi.org/10.1371/journal.pgen.1009985 |
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author | Gupta, Sachin Kumar Jea, Jocelyn Duen-Ya Yen, Laising |
author_facet | Gupta, Sachin Kumar Jea, Jocelyn Duen-Ya Yen, Laising |
author_sort | Gupta, Sachin Kumar |
collection | PubMed |
description | Oncogenic fusion genes as the result of chromosomal rearrangements are important for understanding genome instability in cancer cells and developing useful cancer therapies. To date, the mechanisms that create such oncogenic fusion genes are poorly understood. Previously we reported an unappreciated RNA-driven mechanism in human prostate cells in which the expression of chimeric RNA induces specified gene fusions in a sequence-dependent manner. One fundamental question yet to be addressed is whether such RNA-driven gene fusion mechanism is generalizable, or rather, a special case restricted to prostate cells. In this report, we demonstrated that the expression of designed chimeric RNAs in human endometrial stromal cells leads to the formation of JAZF1-SUZ12, a cancer fusion gene commonly found in low-grade endometrial stromal sarcomas. The process is specified by the sequence of chimeric RNA involved and inhibited by estrogen or progesterone. Furthermore, it is the antisense rather than sense chimeric RNAs that effectively drive JAZF1-SUZ12 gene fusion. The induced fusion gene is validated both at the RNA and the genomic DNA level. The ability of designed chimeric RNAs to drive and recapitulate the formation of JAZF1-SUZ12 gene fusion in endometrial cells represents another independent case of RNA-driven gene fusion, suggesting that RNA-driven genomic recombination is a permissible mechanism in mammalian cells. The results could have fundamental implications in the role of RNA in genome stability, and provide important insight in early disease mechanisms related to the formation of cancer fusion genes. |
format | Online Article Text |
id | pubmed-8722726 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-87227262022-01-04 RNA-driven JAZF1-SUZ12 gene fusion in human endometrial stromal cells Gupta, Sachin Kumar Jea, Jocelyn Duen-Ya Yen, Laising PLoS Genet Research Article Oncogenic fusion genes as the result of chromosomal rearrangements are important for understanding genome instability in cancer cells and developing useful cancer therapies. To date, the mechanisms that create such oncogenic fusion genes are poorly understood. Previously we reported an unappreciated RNA-driven mechanism in human prostate cells in which the expression of chimeric RNA induces specified gene fusions in a sequence-dependent manner. One fundamental question yet to be addressed is whether such RNA-driven gene fusion mechanism is generalizable, or rather, a special case restricted to prostate cells. In this report, we demonstrated that the expression of designed chimeric RNAs in human endometrial stromal cells leads to the formation of JAZF1-SUZ12, a cancer fusion gene commonly found in low-grade endometrial stromal sarcomas. The process is specified by the sequence of chimeric RNA involved and inhibited by estrogen or progesterone. Furthermore, it is the antisense rather than sense chimeric RNAs that effectively drive JAZF1-SUZ12 gene fusion. The induced fusion gene is validated both at the RNA and the genomic DNA level. The ability of designed chimeric RNAs to drive and recapitulate the formation of JAZF1-SUZ12 gene fusion in endometrial cells represents another independent case of RNA-driven gene fusion, suggesting that RNA-driven genomic recombination is a permissible mechanism in mammalian cells. The results could have fundamental implications in the role of RNA in genome stability, and provide important insight in early disease mechanisms related to the formation of cancer fusion genes. Public Library of Science 2021-12-20 /pmc/articles/PMC8722726/ /pubmed/34928964 http://dx.doi.org/10.1371/journal.pgen.1009985 Text en © 2021 Gupta et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Gupta, Sachin Kumar Jea, Jocelyn Duen-Ya Yen, Laising RNA-driven JAZF1-SUZ12 gene fusion in human endometrial stromal cells |
title | RNA-driven JAZF1-SUZ12 gene fusion in human endometrial stromal cells |
title_full | RNA-driven JAZF1-SUZ12 gene fusion in human endometrial stromal cells |
title_fullStr | RNA-driven JAZF1-SUZ12 gene fusion in human endometrial stromal cells |
title_full_unstemmed | RNA-driven JAZF1-SUZ12 gene fusion in human endometrial stromal cells |
title_short | RNA-driven JAZF1-SUZ12 gene fusion in human endometrial stromal cells |
title_sort | rna-driven jazf1-suz12 gene fusion in human endometrial stromal cells |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8722726/ https://www.ncbi.nlm.nih.gov/pubmed/34928964 http://dx.doi.org/10.1371/journal.pgen.1009985 |
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