Alternative splicing in human cells exposed to ionizing radiation: a comprehensive review of ex vivo and in vivo studies

Abstract

Purpose: This study reviews how ionizing radiation (IR) induces alternative splicing (AS) in non-tumor and tumor cells under both ex vivo and in vivo irradiation conditions. The relevance and limitations of IR-induced AS in identifying potential biomarkers are highlighted for two main applications: biodosimetry and radiotherapy. Conclusions: Radiation promotes alterations in AS, which may differentially affect the response in both tumor and non-tumor cells. This response can occur in genes that change their overall expression as well as in those that remain unaltered in response to IR. Although cis-regulators modulate AS, trans-regulators like splicing factors are more involved in the IR response. Variants of key genes involved in the DNA damage response (DDR) are regulated in non-tumor cells while they are often deregulated in tumor cells favoring radioresistance. Identifying IR-induced AS variants could enhance the sensitivity of biodosimeters for dose estimation and biomarkers for radiosensitivity, offering potential strategies to personalize radiotherapy and improve outcomes. New and advanced sequencing technologies will allow variant identification important for the field of radiobiological research.