Differential expression profiles of microRNA in mice internally exposed to tritiated water

Abstract

The adverse effects of tritiated water (HTO) were examined on the differential expression profiles of microRNA in mice. Five groups of mice were injected intraperitoneally with intermediate concentration (5.55 × 10⁵ Bq g⁻¹) of HTO and sacrificed 2, 4, 6, 10, or 28 days after HTO administration. There were also two additional groups of mice injected with either a low (1.85 × 10⁵ Bq g⁻¹) or high (16.65 × 10⁵ Bq g⁻¹) concentration of HTO. The relative expression of mature microRNA genes was determined by microRNA microarray and real-time reverse transcriptase polymerase chain reaction. Gene ontology (GO) analysis was applied to determine the main function of the differentially expressed genes according to the GO. Results showed that intermediate concentration exposure of HTO resulted in six up-regulated and six down-regulated microRNA at day 2, whereas high concentration exposure revealed 11 up-regulated and 14 down-regulated microRNA at day 10, among which miR-34a, miR-26a, and miR-124 may be involved in regulating target genes mediating the HTO-induced response. The GO terms and signaling pathway annotation demonstrated some signaling pathways such as VEGF, MAPK, and TGF-beta which participate in cell proliferation and differentiation. Changes in expression of miR-34a and myc mRNA were correlated, indicating that HTO might affect in vivo pathway of gene expression in liver cells. These results provided new data to link alterations in microRNA expression with adverse effects of HTO-induced radiation.

Keywords:

• HTO
• miRNAs
• GO
• adverse effect

Acknowledgments

Feng-Mei Cui, Xiu-Jin Sun, and Xiang Ding contributed equally to this study. Guang-Liang Bao provided the tritiated water. Liang Sun contributed to the calculation of the cumulative dose. Qiu Chen, Jian-Ping Cao, and Zhao-Hui Ling helped us to analyze the data. The miRCURY LNA™ microRNA array was performed with the assistance of KangCheng Bio-Tech, China. All the authors read and approved the final version of the manuscript. We thank Mr. Ming Xu for his contribution to the writing. The abstract of this manuscript was presented on the XII International Congress of Toxicology held in Barcelona on 19–23 July 2010 and published on Toxicology Letters, Volume 196, Supplement 1, S65–S66. This study was supported by the National Natural Science Foundation of China (81020108028, 30800294) and the Basic Research Project of the Colleges of the Jiangsu Province (08KJD310007).