RNA Splicing, Cell Signaling and Response to Therapies

Cherine Faycal 1 Sylvie Gazzeri 1 Béatrice Eymin 1, *
* Corresponding author
1 Equipe 2 - Bases Moléculaires de la Progression des Cancers du Poumon, Inserm U823
INSERM U823 - Institut d'oncologie/développement Albert Bonniot de Grenoble
Abstract : PURPOSE OF REVIEW: PremRNA alternative splicing is more a rule than an exception as it affects more than 90% of multiexons genes and plays a key role in proteome diversity. Here, we discuss some recent studies published in the extensively growing field linking RNA splicing and cancer. RECENT FINDINGS: These last years, the development of high-throughput studies together with appropriate bioinformatic tools have led to the identification of new cancer-specific splicing patterns that allow to distinguish various cancer types, and provide new prognosis biomarkers. In addition, the functional consequences of hot spot mutations affecting various components of the spliceosome machinery in cancers have been described. As an example, missplicing of the enhancer of zeste homolog 2 histone methyltransferase premRNA in response to hot spot mutation of the splicing factor SRSF2 was found to participate to the pathogenesis of myelodysplastic syndrome. Moreover, proofs of principle that targeting the RNA splicing machinery can be used to correct aberrant missplicing, kill oncogene-driven cancer cells, or reverse resistance of tumor cells to targeted therapies have been done. As another example, the core spliceosomal function was recently found to be critical for the survival of Myc-driven breast cancer cells, rendering them hypersensitive to spliceosome inhibitors. SUMMARY: Dysregulation of premRNA alternative splicing appears to be one of the hallmarks of cancer. The characterization of novel splicing signatures in cancer as well as the identification of original signaling networks involving RNA splicing regulators should allow to decipher novel oncogenic mechanisms and to develop new therapeutic strategies.
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Cherine Faycal, Sylvie Gazzeri, Béatrice Eymin. RNA Splicing, Cell Signaling and Response to Therapies. Current Opinion in Oncology, Lippincott, Williams & Wilkins, 2016, ⟨10.1097/CCO.0000000000000254⟩. ⟨inserm-02337520⟩

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