The role and therapeutic prospects of intercellular communication and RNA m6A modification in radiation-induced liver injury.

Radiation-induced liver injury (RILI) is a common and severe complication of radiotherapy for abdominal and thoracic malignancies. Ionizing radiation triggers widespread alterations of the N6-methyladenosine (m6A) modification landscape of hepatic RNA. Dysregulated m6A methylation disrupts hepatocyte homeostasis, immune cell activation and intercellular communication, and thus may contribute to the progression of RILI from acute inflammation to chronic hepatic fibrosis. Although intercellular crosstalk has been reported in RILI-related studies, its crosstalk with m6A modification remains poorly understood. To date, no dedicated systematic review has elaborated on the m6A modification-dependent mechanisms potentially underlying RILI pathogenesis. Herein, we elaborate the roles of intercellular communication (including cytokine signaling, exosome-mediated crosstalk and immune cell interactions) and m6A modification in RILI pathogenesis. We also summarize the combined regulatory effects for these two pathways on RILI progression, covering inflammation, hepatic fibrosis, liver regeneration and tissue repair. Additionally, we highlight the latest progress in targeted interventions against these pathways, aiming to support the development of novel therapeutic strategies. This review provides a theoretical basis for further investigating the molecular mechanisms of RILI and exploring new treatment modalities.