Title |
Exploring the Significance of the Exon 4-Skipping Isoform of the ZNF217 Oncogene in Breast Cancer
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Published in |
Frontiers in oncology, July 2021
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DOI | 10.3389/fonc.2021.647269 |
Pubmed ID | |
Authors |
Aurélie Bellanger, Diep T. Le, Julie Vendrell, Anne Wierinckx, Lőrinc S. Pongor, Jérôme Solassol, Joël Lachuer, Philippe Clezardin, Balázs Győrffy, Pascale A. Cohen |
Abstract |
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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Geographical breakdown
Country | Count | As % |
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Argentina | 1 | 33% |
Norway | 1 | 33% |
Unknown | 1 | 33% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 2 | 67% |
Scientists | 1 | 33% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 8 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 2 | 25% |
Researcher | 1 | 13% |
Professor > Associate Professor | 1 | 13% |
Student > Bachelor | 1 | 13% |
Student > Postgraduate | 1 | 13% |
Other | 0 | 0% |
Unknown | 2 | 25% |
Readers by discipline | Count | As % |
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Biochemistry, Genetics and Molecular Biology | 3 | 38% |
Unspecified | 1 | 13% |
Pharmacology, Toxicology and Pharmaceutical Science | 1 | 13% |
Design | 1 | 13% |
Unknown | 2 | 25% |