Abstract
Radiation-induced rectal injury is a common side effect of radiotherapy. Hypoxia often occurs after radiotherapy. This study aimed to explore the bystander effect of hypoxia on radiation-induced rectal injury.
In vivo
, apoptosis increased nearby the highly hypoxic area in the rectal tissues in the mouse models of radiation-induced rectal injury, indicating the potential involvement of hypoxia.
In vitro
, flow cytometry and Western blotting showed that both hypoxia and hypoxic human intestinal epithelial crypt (HIEC) cell supernatant promoted apoptosis in normoxic HIEC cells. The pro-apoptotic effect of extracellular vesicles (EVs) derived from hypoxic HIEC cell to normoxic HIEC cells was then determined. MiR-122-5p was chosen for further studies through a microRNA (miRNA) microarray assay and apoptosis was alleviated in cells receiving miR-122-5p inhibiting hypoxic EVs. Together, our study demonstrated that the miR-122-5p containing-EVs derived from hypoxic HIEC cells promoted apoptosis in normoxic HIEC cells. Hypoxic EV-derived miR-122-5p plays a critical pathologic role in radiation-induced rectal injury and may be a potential therapeutic target.