Abstract
Evidence has also shown that micro ribonucleic acid (miRNA) plays an important role in many cellular processes. However, it is unclear how ionizing radiation causes the miRNA and circular ribonucleic acid (circRNA) expression levels to change and how this change relates to esophageal injury. We analyzed RNA Sequencing (RNA-seq) data from normal esophageal tissue and irradiated esophageal tissues and used computational approaches to identify and characterize differentially expressed miRNAs and circRNAs. We detected 27 miRNAs and 197 circRNAs that had significantly different expression levels after ionizing radiation treatment compared with normal control.Among the 27 miRNAs, 7 miRNAs were down-regulated, and the other 20 were up-regulated. Their target genes were found to be involved in responses to wound, lipid biosynthesis, cell proliferation, cell migration, chemokine activity, hairpin binding, and the cell membrane system. We also found 197 differentially expressed circRNAs in total, of which 87 were up-regulated and 110 were down-regulated. Notably, we found that differentially expressed circRNAs were enriched in cell differentiation, epithelial cell migration, striatum development, protein binding, extracellular exosome, and focal adhesion functions. Of the related processes, sphingolipid metabolism was notable. Many of the differentially expressed circRNAs were involved in sphingolipid metabolism pathways. Cells responded to ionizing radiation (IR) using multiple pathways, which led to sphingolipid metabolism and other immune responses, ultimately leading to esophageal injury.IR-induced esophageal injury is worth studying, especially the dynamic network of circRNA and miRNA. By knowing the regulatory details of related pathways, radiation-related esophageal injury can be prevented, and the efficiency of radiation therapy can be enhanced.
Highlights
Radiation therapy, using high dose of radiation to kill tumor cells, is one of the most common and important treatment for cancer
CircRNAs were reported to have the ability to act as the micro ribonucleic acid (miRNA) sponges, which inhibit miRNAs access to their target mRNAs by competing for the same binding site of miRNAs, thereby suppressing the target gene of the respective miRNAs29
Rats with 5 Gy irradiation showed similar body weight increases compared to the control group (0 Gy), whereas 20 Gy-irradiated rats showed a significant decrease in body weight (Fig. 1A)
Summary
Radiation therapy, using high dose of radiation to kill tumor cells, is one of the most common and important treatment for cancer. Indirect action means radiation causes the ionization of water molecules to produce free radicals, which act on important molecules in cells, such as nucleic acids, lipids and proteins, leading to cellular function disorders or even cell death[11]. On the contrast, ionizing radiation induce cells to initiate the transcription and translation of multiple proteins and noncoding RNAs, forming a complex radiation stress-induced regulation network, to defend themselves from the damage caused by radiation[18,19,20]. There is no reports focusing on pathways of intercellular communication and circRNA-miRNA-mRNA network in the radiation-induced injury in esophageal tissues. RNA-seq was used to investigate ionizing radiation-responsive genes in normal esophageal tissue. These analyses provided information for research on radiotherapy that might have a side effect on the esophagus
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