Exploring the significance of the Exon 4-skipping isoform of the ZNF217 oncogene in breast cancer - Université Claude Bernard Lyon 1 Accéder directement au contenu
Article Dans Une Revue Frontiers in Oncology Année : 2021

Exploring the significance of the Exon 4-skipping isoform of the ZNF217 oncogene in breast cancer

Résumé

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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hal-03653025 , version 1 (27-04-2022)

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Aurélie Bellanger, Diep Le, Julie A Vendrell, Anne Wierinckx, Lőrinc Pongor, et al.. Exploring the significance of the Exon 4-skipping isoform of the ZNF217 oncogene in breast cancer. Frontiers in Oncology, 2021, 11, pp.647269. ⟨10.3389/fonc.2021.647269⟩. ⟨hal-03653025⟩
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