Alternative splicing of DNA damage response genes and gastrointestinal cancers

Abstract

Alternative splicing, which is a common phenomenon in mammalian genomes, is a fundamental process of gene regulation and contributes to great protein diversity. Alternative splicing events not only occur in the normal gene regulation process but are also closely related to certain diseases including cancer. In this review, we briefly demonstrate the concept of alternative splicing and DNA damage and describe the association of alternative splicing and cancer pathogenesis, focusing on the potential relationship of alternative splicing, DNA damage, and gastrointestinal cancers. We will also discuss whether alternative splicing leads to genetic instability, which is considered to be a driving force for tumorigenesis. Better understanding of the role and mechanism of alternative splicing in tumorigenesis may provide new directions for future cancer studies.

Keywords: Alternative splicing; DNA damage; Gastrointestinal cancer; Mutation; Genetic instability

Core tip: Alternative splicing is a fundamental process of gene regulation in eukaryotes. Alternative splicing of DNA damage repair proteins is a significant cause of gene mutations, and those mutations in turn affect alternative splicing in cancer. Alternative splicing is associated with tumorigenesis by contributing to genetic instability. Therefore, alternative splicing of DNA damage response-related genes has an important role in tumorigenesis, survival, and growth of gastrointestinal cancers. In summary, the alternative splicing variants of these genes could be potential targets for both diagnosis and treatment of gastrointestinal cancers.