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Radiation-sensitive circRNA promotes intestinal regeneration.

Hui Cai1,2, Xin Liang3, Shazhen Ai4

  • 1Chinese Academy of Medical Sciences & Peking Union Medical College Institute of Radiation Medicine, Tianjin, 300192, China.

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|August 29, 2025
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Summary

A novel circular RNA, circDmbt1(3,4,5,6), acts as a promising biomarker for radiation-induced intestinal injury (RIII). Its expression protects intestinal epithelial cells and promotes regeneration, offering a potential diagnostic and therapeutic target for RIII.

Keywords:
circDmbt1(3,4,5,6)Intestinal stem cellRadiation-induced intestinal injurySTAT3miR-125a-5p

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Area of Science:

  • Molecular Biology
  • Gastroenterology
  • Radiation Oncology

Background:

  • The intestine is highly sensitive to ionizing radiation (IR), leading to radiation-induced intestinal injury (RIII), which significantly impacts patient quality of life.
  • Current diagnostic biomarkers and treatments for RIII are limited, necessitating the identification of new therapeutic targets.
  • Circular RNAs (circRNAs) are implicated in various diseases, but their role in radiation-induced intestinal injury is largely unexplored.

Purpose of the Study:

  • To identify novel circular RNAs involved in radiation-induced intestinal injury.
  • To investigate the function and mechanism of a specific intestine-specific circRNA, circDmbt1(3,4,5,6), in protecting against radiation damage.
  • To evaluate circDmbt1(3,4,5,6) as a potential diagnostic biomarker and therapeutic target for RIII.

Main Methods:

  • RNA sequencing was used to identify differentially expressed circRNAs.
  • In vitro studies explored the effects of circDmbt1(3,4,5,6) on intestinal epithelial cells' proliferation, apoptosis, and DNA damage.
  • Intestinal organoids and a mouse model were utilized to validate the role of circDmbt1(3,4,5,6) in radiation-induced intestinal injury.

Main Results:

  • CircDmbt1(3,4,5,6) was downregulated in mouse intestines post-irradiation and correlated with injury severity.
  • Overexpression of circDmbt1(3,4,5,6) promoted cell proliferation, reduced apoptosis and DNA damage, and enhanced organoid survival after radiation.
  • In vivo, circDmbt1(3,4,5,6) overexpression improved intestinal length, epithelial integrity, and the proportion of key cell types, facilitating intestinal adaptation.

Conclusions:

  • CircDmbt1(3,4,5,6) is a novel, rapidly responding biomarker for early-stage RIII.
  • Exogenous expression of circDmbt1(3,4,5,6) enhances intestinal recovery following radiation damage.
  • The circDmbt1(3,4,5,6)/miR-125a-5p/STAT3 axis is crucial for intestinal epithelial regeneration after radiation, presenting a potential diagnostic and therapeutic strategy for RIII.