Skip to Main content Skip to Navigation
Journal articles

A dedicated microarray for in-depth analysis of pre-mRNA splicing events: application to the study of genes involved in the response to targeted anticancer therapies.

Marine Pesson 1 Béatrice Eymin 2 Pierre de la Grange 3 Brigitte Simon 1 Laurent Corcos 1, *
* Corresponding author
1 Inserm U1078, équipe ECLA
GGB - Génétique, génomique fonctionnelle et biotechnologies (UMR 1078)
2 Equipe 2 - Bases Moléculaires de la Progression des Cancers du Poumon, Inserm U823
INSERM U823 - Institut d'oncologie/développement Albert Bonniot de Grenoble
Abstract : : Alternative pre-mRNA splicing (AS) widely expands proteome diversity through the combinatorial assembly of exons. The analysis of AS on a large scale, by using splice-sensitive microarrays, is a highly efficient method to detect the majority of known and predicted alternative transcripts for a given gene. The response to targeted anticancer therapies cannot easily be anticipated without prior knowledge of the expression, by the tumor, of target proteins or genes. To analyze, in depth, transcript structure and levels for genes involved in these responses, including AKT1-3, HER1-4, HIF1A, PIK3CA, PIK3R1-2, VEGFA-D and PIR, we engineered a dedicated gene chip with coverage of an average 185 probes per gene and, especially, exon-exon junction probes. As a proof of concept, we demonstrated the ability of such a chip to detect the effects of over-expressed SRSF2 RNA binding protein on the structure and abundance of mRNA products in H538 lung cancer cells conditionally over-expressing SRSF2. Major splicing changes were observed, including in HER1/EGFR pre-mRNA, which were also seen in human lung cancer samples over-expressing the SRSF2 protein. In addition, we showed that variations in HER1/EGFR pre-mRNA splicing triggered by SRSF2 overexpression in H358 cells resulted in a drop in HER1/EGFR protein level, which correlated with increased sensitivity to gefitinib, an EGFR tyrosine kinase inhibitor. We propose, therefore, that this novel tool could be especially relevant for clinical applications, with the aim to predict the response before treatment.
Complete list of metadatas

Cited literature [47 references]  Display  Hide  Download

https://www.hal.inserm.fr/inserm-00935318
Contributor : Ed. Bmc <>
Submitted on : Thursday, January 23, 2014 - 1:15:21 PM
Last modification on : Wednesday, August 19, 2020 - 11:17:04 AM
Long-term archiving on: : Thursday, April 24, 2014 - 12:00:30 PM

Files

1476-4598-13-9.pdf
Publisher files allowed on an open archive

Identifiers

Collections

Citation

Marine Pesson, Béatrice Eymin, Pierre de la Grange, Brigitte Simon, Laurent Corcos. A dedicated microarray for in-depth analysis of pre-mRNA splicing events: application to the study of genes involved in the response to targeted anticancer therapies.. Molecular Cancer, BioMed Central, 2014, 13 (1), pp.9. ⟨10.1186/1476-4598-13-9⟩. ⟨inserm-00935318⟩

Share

Metrics

Record views

1587

Files downloads

810