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Targeting AP-1 transcription factors by CRISPR in the prostate

Prostate cancer is the second most diagnosed cancer in men. It is a slow progressing cancer, but when the disease reaches an advanced stage, treatment options are limited. Sequencing analyses of cancer samples have identified genes that can potentially drive disease progression. We implemented the C...

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Autores principales: Riedel, Maria, Cai, Huiqiang, Stoltze, Iben C., Vendelbo, Mikkel H., Wagner, Erwin F., Bakiri, Latifa, Thomsen, Martin K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8448511/
https://www.ncbi.nlm.nih.gov/pubmed/34548912
http://dx.doi.org/10.18632/oncotarget.27997
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author Riedel, Maria
Cai, Huiqiang
Stoltze, Iben C.
Vendelbo, Mikkel H.
Wagner, Erwin F.
Bakiri, Latifa
Thomsen, Martin K.
author_facet Riedel, Maria
Cai, Huiqiang
Stoltze, Iben C.
Vendelbo, Mikkel H.
Wagner, Erwin F.
Bakiri, Latifa
Thomsen, Martin K.
author_sort Riedel, Maria
collection PubMed
description Prostate cancer is the second most diagnosed cancer in men. It is a slow progressing cancer, but when the disease reaches an advanced stage, treatment options are limited. Sequencing analyses of cancer samples have identified genes that can potentially drive disease progression. We implemented the CRISPR/Cas9 technology to simultaneously manipulate multiple genes in the murine prostate and thus to functionally test putative cancer driver genes in vivo. The activating protein-1 (AP-1) transcription factor is associated with many different cancer types, with the proto-oncogenes JUN and FOS being the two most intensely studied subunits. We analyzed expression of FOS and JUNB in human prostate cancer datasets and observed decreased expression in advanced stages. By applying CRISPR/Cas9 technology, the role of these two transcription factors in prostate cancer progression was functionally tested. Our data revealed that loss of either JunB or Fos in the context of Pten loss drives prostate cancer progression to invasive disease. Furthermore, loss of Fos increases Jun expression, and CRISPR inactivation of Jun in this context decreases cell proliferation. Overall, these in vivo studies reveal that JunB and Fos exhibit a tumor suppressor function by repressing invasive disease, whereas Jun is oncogenic and increases cell proliferation. This demonstrates that AP-1 factors are implicated in prostate cancer progression at different stages and display a dual function as tumor suppressor and as an oncogene in cancer progression.
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spelling pubmed-84485112021-09-20 Targeting AP-1 transcription factors by CRISPR in the prostate Riedel, Maria Cai, Huiqiang Stoltze, Iben C. Vendelbo, Mikkel H. Wagner, Erwin F. Bakiri, Latifa Thomsen, Martin K. Oncotarget Research Perspective Prostate cancer is the second most diagnosed cancer in men. It is a slow progressing cancer, but when the disease reaches an advanced stage, treatment options are limited. Sequencing analyses of cancer samples have identified genes that can potentially drive disease progression. We implemented the CRISPR/Cas9 technology to simultaneously manipulate multiple genes in the murine prostate and thus to functionally test putative cancer driver genes in vivo. The activating protein-1 (AP-1) transcription factor is associated with many different cancer types, with the proto-oncogenes JUN and FOS being the two most intensely studied subunits. We analyzed expression of FOS and JUNB in human prostate cancer datasets and observed decreased expression in advanced stages. By applying CRISPR/Cas9 technology, the role of these two transcription factors in prostate cancer progression was functionally tested. Our data revealed that loss of either JunB or Fos in the context of Pten loss drives prostate cancer progression to invasive disease. Furthermore, loss of Fos increases Jun expression, and CRISPR inactivation of Jun in this context decreases cell proliferation. Overall, these in vivo studies reveal that JunB and Fos exhibit a tumor suppressor function by repressing invasive disease, whereas Jun is oncogenic and increases cell proliferation. This demonstrates that AP-1 factors are implicated in prostate cancer progression at different stages and display a dual function as tumor suppressor and as an oncogene in cancer progression. Impact Journals LLC 2021-09-14 /pmc/articles/PMC8448511/ /pubmed/34548912 http://dx.doi.org/10.18632/oncotarget.27997 Text en Copyright: © 2021 Riedel et al. https://creativecommons.org/licenses/by/3.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Perspective
Riedel, Maria
Cai, Huiqiang
Stoltze, Iben C.
Vendelbo, Mikkel H.
Wagner, Erwin F.
Bakiri, Latifa
Thomsen, Martin K.
Targeting AP-1 transcription factors by CRISPR in the prostate
title Targeting AP-1 transcription factors by CRISPR in the prostate
title_full Targeting AP-1 transcription factors by CRISPR in the prostate
title_fullStr Targeting AP-1 transcription factors by CRISPR in the prostate
title_full_unstemmed Targeting AP-1 transcription factors by CRISPR in the prostate
title_short Targeting AP-1 transcription factors by CRISPR in the prostate
title_sort targeting ap-1 transcription factors by crispr in the prostate
topic Research Perspective
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8448511/
https://www.ncbi.nlm.nih.gov/pubmed/34548912
http://dx.doi.org/10.18632/oncotarget.27997
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