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Exploring the Significance of the Exon 4-Skipping Isoform of the ZNF217 Oncogene in Breast Cancer

Oncogene alternative splicing events can create distinct functional transcripts that offer new candidate prognostic biomarkers for breast cancer. ZNF217 is a well-established oncogene but its exon 4-skipping isoform (ZNF217-ΔE4) has never been investigated in terms of clinical or biological relevanc...

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Autores principales: Bellanger, Aurélie, Le, Diep T., Vendrell, Julie, Wierinckx, Anne, Pongor, Lőrinc S., Solassol, Jérôme, Lachuer, Joël, Clezardin, Philippe, Győrffy, Balázs, Cohen, Pascale A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8283766/
https://www.ncbi.nlm.nih.gov/pubmed/34277402
http://dx.doi.org/10.3389/fonc.2021.647269
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author Bellanger, Aurélie
Le, Diep T.
Vendrell, Julie
Wierinckx, Anne
Pongor, Lőrinc S.
Solassol, Jérôme
Lachuer, Joël
Clezardin, Philippe
Győrffy, Balázs
Cohen, Pascale A.
author_facet Bellanger, Aurélie
Le, Diep T.
Vendrell, Julie
Wierinckx, Anne
Pongor, Lőrinc S.
Solassol, Jérôme
Lachuer, Joël
Clezardin, Philippe
Győrffy, Balázs
Cohen, Pascale A.
author_sort Bellanger, Aurélie
collection PubMed
description Oncogene alternative splicing events can create distinct functional transcripts that offer new candidate prognostic biomarkers for breast cancer. ZNF217 is a well-established oncogene but its exon 4-skipping isoform (ZNF217-ΔE4) has never been investigated in terms of clinical or biological relevance. Using in silico RNA-seq and RT-qPCR analyses, we demonstrated for the first time the existence of ZNF217-ΔE4 transcripts in primary breast tumors, and a positive correlation between ZNF217-ΔE4 mRNA levels and those of the wild-type oncogene (ZNF217-WT). A pilot retrospective analysis revealed that, in the Luminal subclass, the combination of the two ZNF217 variants (the ZNF217-ΔE4-WT gene-expression signature) provided more information than the mRNA expression levels of each isoform alone. Ectopic overexpression of ZNF217-ΔE4 in breast cancer cells promoted an aggressive phenotype and an increase in ZNF217-WT expression levels that was inversely correlated with DNA methylation of the ZNF217 gene. This study provides new insights into the possible role of the ZNF217-ΔE4 splice variant in breast cancer and suggests a close interplay between the ZNF217-WT and ZNF217-ΔE4 isoforms. Our data suggest that a dual signature combining the expression levels of these two isoforms may serve as a novel prognostic biomarker allowing better stratification of breast cancers with good prognosis and aiding clinicians in therapeutic decisions.
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spelling pubmed-82837662021-07-17 Exploring the Significance of the Exon 4-Skipping Isoform of the ZNF217 Oncogene in Breast Cancer Bellanger, Aurélie Le, Diep T. Vendrell, Julie Wierinckx, Anne Pongor, Lőrinc S. Solassol, Jérôme Lachuer, Joël Clezardin, Philippe Győrffy, Balázs Cohen, Pascale A. Front Oncol Oncology Oncogene alternative splicing events can create distinct functional transcripts that offer new candidate prognostic biomarkers for breast cancer. ZNF217 is a well-established oncogene but its exon 4-skipping isoform (ZNF217-ΔE4) has never been investigated in terms of clinical or biological relevance. Using in silico RNA-seq and RT-qPCR analyses, we demonstrated for the first time the existence of ZNF217-ΔE4 transcripts in primary breast tumors, and a positive correlation between ZNF217-ΔE4 mRNA levels and those of the wild-type oncogene (ZNF217-WT). A pilot retrospective analysis revealed that, in the Luminal subclass, the combination of the two ZNF217 variants (the ZNF217-ΔE4-WT gene-expression signature) provided more information than the mRNA expression levels of each isoform alone. Ectopic overexpression of ZNF217-ΔE4 in breast cancer cells promoted an aggressive phenotype and an increase in ZNF217-WT expression levels that was inversely correlated with DNA methylation of the ZNF217 gene. This study provides new insights into the possible role of the ZNF217-ΔE4 splice variant in breast cancer and suggests a close interplay between the ZNF217-WT and ZNF217-ΔE4 isoforms. Our data suggest that a dual signature combining the expression levels of these two isoforms may serve as a novel prognostic biomarker allowing better stratification of breast cancers with good prognosis and aiding clinicians in therapeutic decisions. Frontiers Media S.A. 2021-07-02 /pmc/articles/PMC8283766/ /pubmed/34277402 http://dx.doi.org/10.3389/fonc.2021.647269 Text en Copyright © 2021 Bellanger, Le, Vendrell, Wierinckx, Pongor, Solassol, Lachuer, Clezardin, Győrffy and Cohen https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Bellanger, Aurélie
Le, Diep T.
Vendrell, Julie
Wierinckx, Anne
Pongor, Lőrinc S.
Solassol, Jérôme
Lachuer, Joël
Clezardin, Philippe
Győrffy, Balázs
Cohen, Pascale A.
Exploring the Significance of the Exon 4-Skipping Isoform of the ZNF217 Oncogene in Breast Cancer
title Exploring the Significance of the Exon 4-Skipping Isoform of the ZNF217 Oncogene in Breast Cancer
title_full Exploring the Significance of the Exon 4-Skipping Isoform of the ZNF217 Oncogene in Breast Cancer
title_fullStr Exploring the Significance of the Exon 4-Skipping Isoform of the ZNF217 Oncogene in Breast Cancer
title_full_unstemmed Exploring the Significance of the Exon 4-Skipping Isoform of the ZNF217 Oncogene in Breast Cancer
title_short Exploring the Significance of the Exon 4-Skipping Isoform of the ZNF217 Oncogene in Breast Cancer
title_sort exploring the significance of the exon 4-skipping isoform of the znf217 oncogene in breast cancer
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8283766/
https://www.ncbi.nlm.nih.gov/pubmed/34277402
http://dx.doi.org/10.3389/fonc.2021.647269
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