Hallmarks of Splicing Defects in Cancer: Clinical Applications in the Era of Personalized Medicine

Rahman, M.A., Nasrin, F., Bhattacharjee, S., Nandi, S. (May 2020) Hallmarks of Splicing Defects in Cancer: Clinical Applications in the Era of Personalized Medicine. Cancers (Basel), 12 (6). E1381. ISSN 2072-6694

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Abstract

Alternative splicing promotes proteome diversity by using limited number of genes, a key control point of gene expression. Splicing is carried out by large macromolecular machineries, called spliceosome, composed of small RNAs and proteins. Alternative splicing is regulated by splicing regulatory cis-elements in RNA and trans-acting splicing factors that are often tightly regulated in a tissue-specific and developmental stage-specific manner. The biogenesis of ribonucleoprotein (RNP) complexes is strictly regulated to ensure that correct complements of RNA and proteins are coordinated in the right cell at the right time to support physiological functions. Any perturbations that impair formation of functional spliceosomes by disrupting the cis-elements, or by compromising RNA-binding or function of trans-factors can be deleterious to cells and result in pathological consequences. The recent discovery of oncogenic mutations in splicing factors, and growing evidence of the perturbed splicing in multiple types of cancer, underscores RNA processing defects as a critical driver of oncogenesis. These findings have resulted in a growing interest in targeting RNA splicing as a therapeutic approach for cancer treatment. This review summarizes our current understanding of splicing alterations in cancer, recent therapeutic efforts targeting splicing defects in cancer, and future potentials to develop novel cancer therapies.

Item Type:	Paper
Subjects:	bioinformatics diseases & disorders > cancer bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification diseases & disorders bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics therapies bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > Alternative Splicing therapies > personalised therapy
CSHL Authors:	Rahman, Mohammad Bhattacharjee, Sonali Nandi, Saikat Nasrin, Farhana
Depositing User:	Adrian Gomez
Date:	28 May 2020
Date Deposited:	05 Jun 2020 13:49
Last Modified:	01 Feb 2024 16:56
PMCID:	PMC7352608
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/39489

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