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Changes in patient peripheral blood cell microRNAs after total body irradiation during hematopoietic stem cell
Juan-Juan Li1, Lei Xu2, Cheng-Long Wang3
1Laboratory of Tissue Regeneration and Immunology and Department of Periodontics, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing, China.
Background:
Ionizing radiation exposure is a great threat to human health. MicroRNAs (miRNAs) have been shown to play an important role in radiation-induced biological effects. Here, we investigated plasma miRNA expression changes and differentially expressed miRNAs in radiotherapy patients exposed to cobalt-60 (60Co) gamma rays to provide an experimental basis for human plasma miRNAs as an estimation indicator for ionizing radiation injury.
Methods:
Six patients with acute lymphoblastic leukemia (ALL) received continuous 5 gray (Gy) total body irradiation (TBI) twice. At 12 hours after irradiation, miRNA microarray was applied to screen for differentially expressed miRNAs, with some miRNAs confirmed by real-time polymerase chain reaction (RT-PCR) assay. Bioinformatic analysis was carried out to identify the relevant target genes and biological function of the differentially expressed miRNAs.
Results:
After radiotherapy patients were exposed to 5 Gy gamma radiation, the expression of 9 plasma miRNAs was significantly upregulated, and the expression of 2 miRNAs was downregulated. After irradiation with 10 Gy gamma radiation, the blood plasma of radiotherapy patients contained 18 differentially expressed miRNAs, of which 17 were upregulated and 1 was downregulated (P<0.05). The expression of miR-4532, miR-4634, miR-4655-5p, miR-4763-3p, miR-4785, miR-6087, miR-6850-5p, and miR-6869-5p were significantly upregulated in both the 5-Gy and 10-Gy dose groups, showing a certain dose-response relationship. The RT-PCR results were consistent with the findings of high-throughput sequencing. In addition, the target genes of the differentially expressed miRNAs were mainly involved in RNA transcription and DNA damage. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that these miRNAs participated in phosphoinositide 3-kinase/protein kinase B (PI3K/AKT), Ras, mitogen-activated protein kinase (MAPK), and other signaling pathways.
Conclusions:
The expression of differential plasma miRNAs of radiotherapy patients was associated with irradiation injury and showed a certain dose-effect relationship. These differentially coexpressed plasma miRNAs could be used as an early indicator for estimating radiation injury.
