Identification of Circular RNAs Altered in Mouse Jejuna After Radiation

Cell Physiol Biochem. 2018;47(6):2558-2568. doi: 10.1159/000491652. Epub 2018 Jul 10.

Abstract

Background/aims: Circular RNAs (circRNAs) make up a large class of non-coding RNAs and play important roles in a variety of diseases, including nervous system diseases and cancers. The intestinal epithelium is sensitive to ionizing radiation, radiotherapy of abdominal or pelvic tumors or nuclear accident exposure can lead to high radiation toxicity, which can result in radiation-induced intestinal injury. The goal of this present study was to analyze the potential roles of circRNAs in radiation-induced intestinal injury.

Methods: Mice were divided into two groups: control group and irradiated group. Irradiated group was 3.5 days after 14Gy abdominal irradiation (ABI) group. We started with RNA-seq of circRNA changes in mouse jejuna after radiation and validated by RT-PCR in the following experimental. miRNAs targeted mRNAs were predicted using proprietary software based on target scan and Miranda. The network of circRNA-miRNA-mRNA was illustrated by cytoscape software.

Results: 2751 circRNAs were detected in the two groups. At day 3.5 post-radiation, 42 and 48 circRNAs were found to be significantly upregulated and downregulated, respectively, compared to the control (p≤0.05, Fold Change ≥2). Further, the altered expression of 10 circRNAs (chr18: 35610871-35613502+, chr15: 95864225-95894541+, chr3: 96041338-96042928-, chr5: 64096979-64108263+, chr19: 16705875-16710941-, chr5: 134491893-134500149-, chr19: 42562552-42564341+, chr5: 32640331-32664400+, chr3: 72958113-72960367- and chr8: 79343654-79372364-) were verified by RT-PCR. Compared the miRNA-targeted mRNAs with our mRNAs sequencing data, we found 14 upregulated circRNA-targeted mRNAs were also unregulated and 22 downregulated circRNAs-targeted mRNAs were also downregulated. Gene ontology and KEGG pathway analyses indicated the predicted genes were mainly involved in the MAPK signaling pathway.

Conclusions: This study reveals that expression of circRNAs was altered in the jejuna of mice post-irradiation and provides a resource for the study of circRNAs in radiation-induced intestinal injury and repair.

Keywords: CircRNAs; Radiation-induced intestinal injury; Sequencing.

MeSH terms

  • Animals
  • Jejunal Diseases / metabolism*
  • Jejunal Diseases / pathology
  • Jejunum / metabolism*
  • Jejunum / pathology
  • MAP Kinase Signaling System*
  • Male
  • Mice
  • RNA, Untranslated / metabolism*
  • Radiation Injuries, Experimental / metabolism*
  • Radiation Injuries, Experimental / pathology

Substances

  • RNA, Untranslated