Splicing and cancer: Challenges and opportunities

Cancer arises from alterations in several metabolic processes affecting proliferation, growth, replication and death of cells. A fundamental challenge in the study of cancer biology is to uncover molecular mechanisms that lead to malignant cellular transformation. Recent genomic analyses revealed that many molecular alterations observed in cancers come from modifications in the splicing process, including mutations in pre‐mRNA regulatory sequences, mutations in spliceosome components, and altered ratio of specific splicing regulators. While alterations in splice site preferences might generate alternative isoforms enabling different biological functions, these might also be responsible for nonfunctional isoforms that can eventually cause dysregulation in cellular processes. Molecular characteristics of regulatory sequences and proteins might also be important prognostic tools revealing a cancer‐specific splicing pattern and linking splicing control to cancer development. The connection between cancer biology and splicing regulation is of primary importance to understand the mechanisms leading to disease and also to improve development of therapeutic approaches. Splicing modulation is being explored in new anti‐cancer therapies and further investigation of targeted splicing factors is critical for the success of these strategies. This article is categorized under: RNA Processing > Splicing Mechanisms RNA‐Based Catalysis > RNA Catalysis in Splicing and Translation RNA Processing > Splicing Regulation/Alternative Splicing RNA in Disease and Development > RNA in Disease Cancer cells have specific splicing patterns defined by spliceosomal proteins, cis‐regulatory elements, and availability of regulatory proteins. Cellular phenotype will be defined by this pattern, affecting cellular proliferation, growth, migration and death, ultimately leading or not to malignant transformation.