Abstract 5389: Circulating miRNAs as potential targets for the protection of radiation-induced immunologic injury
Authors: Heng Zhou, Wenjun Wei, Jufang Wang
Journal: Cancer Research (2018)

Abstract MicroRNAs (miRNAs) are non-coding RNAs of 19-22 nucleotides which regulate a diverse set of physiological processes including immune cell development by post-transcriptional gene regulation. Circulating miRNAs in blood have been assessed as biomarkers of disease diagnosis and are capable of modulating a wide-range of biological functions through targeting the molecules of recipient cells. In our previous work, some radiosensitive circulating miRNAs have been identified, and most of them were closely associated with immune and hematopoietic system. Here, we further investigated the effects of radioprotector on the changes of miRNA expression levels after exposure of mice to X-rays or carbon ion beam, aiming to explore novel potential therapeutic targets. Kunming mice were whole-body exposed to 2 and 4 Gy of X-rays generated by Faxitron RX650 or 0.1 and 0.5 Gy of carbon ion beam generated by the HIRFL (Institute of Modern Physics, Lanzhou, China). Angelica sinensis polysaccharide (ASP) which is able to promote the hematopoietic function in vivo and GANRA agent which can scavenge the ROS were administrated to mice by gavage for 7 days before exposure. The expression of circulating miRNAs were detected by qRT-PCR analysis. Our results confirmed that ASP significantly protected the immune and hematopoietic systems of irradiated mice by recovering the numbers of bone marrow hematopoietic cells, peripheric leucocytes, lymphocytes and atrophy of the spleen. GANRA increased the number of lymphocytes, leucocytes and the ratio of CD4+/CD8+ cells in the spleen of irradiated mice. Moreover, GANRA could eliminate ROS which was produced by X-rays and carbon ion beam, and increased the cell viability. Meanwhile, the expression levels of circulating miRNAs such as let-7a, miR-34a, miR-223, miR-150 and miR-574 were distinctively different between ASP or GANRA treated and the control group. ASP or GANRA treatment could rescue the up-regulation of let-7a, miR-34a and miR-223, and the down-regulation of miR-150 and miR-574 that were induced by radiation, indicating that circulating miRNAs could be possible targets of radioprotector responding to radiation exposure. In conclusion, ASP and GANRA treatments have significant protective effects on the immune and hematopoietic system. The differential expressions of circulating miRNAs in radioprotector treated and non-treated groups indicate that miRNAs are potential targets for the protection of radiation-induced immunologic injury. By further exploring the function of these miRNA and their influence on the immune and hematopoietic systems, it will accelerate the development of new biomarkers and drug targets. Citation Format: Heng Zhou, Wenjun Wei, Jufang Wang. Circulating miRNAs as potential targets for the protection of radiation-induced immunologic injury [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5389.