Long non-coding RNA H19 affects the inflammatory response in radiation-induced intestinal injury through miR-130b-3p

Radiation-induced intestinal injury (RIII) is a common complication of abdominal and pelvic radiotherapy, and remains a major clinical challenge due to the lack of effective therapeutic interventions. Although long non-coding RNAs (lncRNAs) are recognized as critical regulators of intestinal pathophysiology, their specific involvement in RIII pathogenesis remains unexplored. In this study, we established a radiation damage model in mouse and MODE-K cell to investigate the role and mechanism of lncRNA H19 both in vivo and in vitro. Quantitative analysis revealed a significant upregulation of H19 in irradiated intestinal tissues and MODE-K cells. In vivo genetic suppression of H19 substantially ameliorated radiation-induced intestinal pathology and preserved crypt-villus architecture. Consistently, in vitro knockdown of H19 in MODE-K cells conferred cytoprotective effects against radiation exposure, as evidenced by enhanced proliferative capacity, reduced apoptosis, and attenuated DNA damage. Conversely, H19 overexpression exacerbated radiation cytotoxicity, establishing its functional role in cellular radiosensitivity. Mechanistically, the effect of H19 may be mediated through the regulation of miR-130b-3p and tumor necrosis factor-α (TNF-α) expression. Collectively, our study is the first to identify H19 as a key mediator of RIII and to demonstrate that targeting H19 represents a promising therapeutic strategy. These findings provide novel mechanistic insights into the pathogenesis of RIII and offer a potential target for clinical intervention.