| Cai Dan,Fan Ying,Mo Yunqi,et al.Anti-radiation effects of gene CCND1 activated by low-dose radiation[J].Chinese Journal of Radiological Medicine and Protection,2025,45(9):840-850 |
| Anti-radiation effects of gene CCND1 activated by low-dose radiation |
| Received:January 20, 2025 |
| DOI：10.3760/cma.j.cn112271-20250120-00027 |
| KeyWords:Low dose radiation Adaptive response CCND1 Radiation resistance |
| FundProject:国家自然科学基金面上项目(32271282);国家自然科学基金青年科学基金(82003394) |
| Author Name | Affiliation | E-mail | | Cai Dan | Graduate Collaborative Training Base of Academy of Military Sciences, Hengyang Medical School, University of South China, Hengyang 421001, China
Academy of Military Medical Sciences, Beijing 100850, China | | | Fan Ying | Academy of Military Medical Sciences, Beijing 100850, China | | | Mo Yunqi | Graduate Collaborative Training Base of Academy of Military Sciences, Hengyang Medical School, University of South China, Hengyang 421001, China
Academy of Military Medical Sciences, Beijing 100850, China | | | Liu Ruixue | Academy of Military Medical Sciences, Beijing 100850, China | | | Wu Lei | Academy of Military Medical Sciences, Beijing 100850, China | | | Ma Jianan | Academy of Military Medical Sciences, Beijing 100850, China | | | Wang Qi | Academy of Military Medical Sciences, Beijing 100850, China | | | Qi Zhenhua | Academy of Military Medical Sciences, Beijing 100850, China | | | Wang Zhidong | Graduate Collaborative Training Base of Academy of Military Sciences, Hengyang Medical School, University of South China, Hengyang 421001, China
Academy of Military Medical Sciences, Beijing 100850, China | wangzhidong1977@126.com |
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| Abstract:: |
| Objective To select low-dose radiation-activated genes with intrinsic radiation protection by developing a model for adaptive responses to low-dose ionizing radiation, in order to explore the mechanisms behind the radiation resistance of the candidate genes. Methods The cells were divided into adaptive response induction group and whole transcriptome sequencing group. The level of DNA damage was assessed using the γ-H2AX immunofluorescence assay. The low-dose radiation-activated candidate genes with radiation protection were selected through whole transcriptome sequencing and quantitative reverse transcription PCR (RT-qPCR)-based validation. The anti-radiation effect of candidate gene CCND1 was assessed based on CCK-8 cell proliferation and γ-H2AX immunofluorescence assay. After up- and down-regulation of CCND1 expression, the anti-radiation mechanism of CCND1 was preliminarily explored through transcriptome sequencing analysis. Results A model for low-dose ionizing radiation-induced adaptive responses of lymphocytes was constructed. Using this model, six candidate genes with radiation protection, including CCND1, ZMAT3, MGAT3, DFFB, CYP4F2, ITGA6, were selected. Compared to the control group, overexpressed CCND1 led to significantly enhanced proliferation ability of AHH-1 cells (t = 7.92-14.76, P < 0.05) and distinctly lowered level of DNA damage (t = 2.79-9.68, P < 0.05) after 2 Gy of X-ray irradiation. Furthermore, compared to the control group, the CCND1 knockdown caused significantly decreased cell proliferation ability (t = 13.58-26.25, P < 0.05) and notably elevated level of DNA damage of cells (t = 2.87-7.61, P < 0.05). Transcriptome sequencing revealed that up- and down-regulation of CCND1 expression resulted in the activation of pathways related to cell growth, death, and damage repair. Conclusions By selecting six low-dose-activated candidate genes with radiation protection and revealing the function of CCND1 in radiation protection, this study provides a new perspective for the development of radiation protection agents from the perspective of adaptive responses to low-dose radiation. |
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