| Wu Zhizhou,Wang Chenyu,Xiao Yunhua,et al.Inhibiting AURKA exacerbates mitotic catastrophe and enhances radiosensitivity of hepatocellular carcinoma cells to 125I seeds[J].Chinese Journal of Radiological Medicine and Protection,2026,46(5):504-512 |
| Inhibiting AURKA exacerbates mitotic catastrophe and enhances radiosensitivity of hepatocellular carcinoma cells to 125I seeds |
| Received:November 10, 2025 |
| DOI：10.3760/cma.j.cn112271-20251110-00394 |
| KeyWords:Hepatocellular carcinoma 125I Mitotic catastrophe Aurora kinase A Radiosensitivity |
| FundProject:重庆市自然科学基金(CSTB2022NSCQ-MSX1501,CSTB2023NSCQ-MSX0600,CSTB2024NSCQ-KJFZMSX0038) |
| Author Name | Affiliation | E-mail | | Wu Zhizhou | Department of Nuclear Medicine, First Affiliated Hospital of Army Medical University, Chongqing 400038, China | | | Wang Chenyu | Department of Nuclear Medicine, First Affiliated Hospital of Army Medical University, Chongqing 400038, China | | | Xiao Yunhua | Department of Nuclear Medicine, First Affiliated Hospital of Army Medical University, Chongqing 400038, China | | | Xiong Junru | Department of Nuclear Medicine, First Affiliated Hospital of Army Medical University, Chongqing 400038, China | | | Deng Liangyu | Department of Nuclear Medicine, First Affiliated Hospital of Army Medical University, Chongqing 400038, China | | | Li Liangshan | Department of Nuclear Medicine, First Affiliated Hospital of Army Medical University, Chongqing 400038, China | | | He Chuang | Department of Nuclear Medicine, First Affiliated Hospital of Army Medical University, Chongqing 400038, China | | | Huang Xuequan | Department of Nuclear Medicine, First Affiliated Hospital of Army Medical University, Chongqing 400038, China | huangxq68@tmmu.edu.cn |
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| Abstract:: |
| Objective To investigate the correlation between Aurora kinase A (AURKA) and the radiosensitivity of hepatocellular carcinoma (HCC) cells to 125I seeds, and to explore the potential molecular mechanism. Methods Morphological changes of HCC HUH7 cells after 125I seed irradiation were observed by immunofluorescence. The GeneCard, iProX and GENEMANIA databases were used to screen core genes for radiosensitization by 125I radiotherapy and perform functional annotation. An AURKA-knockdown HUH7 cell line was constructed, and cell colony-forming ability was assessed by plate colony formation assay. HUH7 cells were divided into control group, MLN8237 group (0.8 μmol/L, 72 h), 125I group (6 Gy), and MLN8237 + 125I group. Immunofluorescence, Western blot, plate colony formation, and flow cytometry were used to detect γ-H2AX expression, cell proliferation and colony formation, mitotic catastrophe rate, and apoptosis, respectively. Results Immunofluorescence showed that 125I seed irradiation induced mitotic catastrophe in HCC cells. Analysis of GeneCard, iProX, and GENEMANIA databases indicated that AURKA was associated with mitotic regulation and poor prognosis in HCC (overall survival: HR=1.9, 95% CI: 1.2-2.8; disease-free survival: HR=1.6, 95% CI: 1.1-2.3, P<0.05). The iProX database suggested that AURKA might be involved in the regulation of mitotic catastrophe induced by 125I irradiation. Compared with the control group, AURKA knockdown significantly reduced the proliferation and colony-forming ability of HCC cells (t=10.15, P<0.05). Compared with the 125I group, the number of γ-H2AX foci (t=5.76, P<0.05) and γ-H2AX protein expression (t=16.26, P<0.05) were significantly increased in the MLN8237 + 125I group. Compared with the NC-SH+125I group, the SH-AURKA+125I group exhibited a significantly increased mitotic catastrophe rate (t=7.76, P<0.05). Compared with the 125I group, the MLN8237+125I group showed significantly increased mitotic catastrophe and apoptosis rates (t=10.39 and 6.27, respectively; P< 0.05). Conclusion High AURKA expression is associated with poor prognosis in liver cancer. Knockdown or pharmacological inhibition of AURKA by MLN8237 enhances the radiosensitivity of liver cancer cells to 125I seeds by exacerbating DNA double-strand breaks and increasing the mitotic catastrophe rate. |
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