| Ma Yanli,Wang Jialin,Ma Rong,et al.Experimental study on UBQLN2 induced-radioresistance in esophageal squamous cell carcinoma cells by upregulating purine metabolism levels[J].Chinese Journal of Radiological Medicine and Protection,2024,44(11):909-916 |
| Experimental study on UBQLN2 induced-radioresistance in esophageal squamous cell carcinoma cells by upregulating purine metabolism levels |
| Received:February 20, 2024 |
| DOI：10.3760/cma.j.cn112271-20240220-00065 |
| KeyWords:Esophageal squamous cell carcinoma (ESCC) UBQLN2 Radiosensitivity Purine metabolism |
| FundProject:国家自然科学基金(82060433);宁夏自然科学基金(2021AAC05018) |
| Author Name | Affiliation | E-mail | | Ma Yanli | Department of Radiotherapy, Cancer Hospital, the General Hospital of Ningxia Medical University, Yinchuan 750001, China
Department of Gerontology, 2nd People's Hospital of Shizuishan, Shizuishan 753000, China | | | Wang Jialin | Department of Radiotherapy, Cancer Hospital, the General Hospital of Ningxia Medical University, Yinchuan 750001, China | | | Ma Rong | Department of Radiotherapy, Cancer Hospital, the General Hospital of Ningxia Medical University, Yinchuan 750001, China | | | Pan Wenyan | Department of Radiotherapy, Cancer Hospital, the General Hospital of Ningxia Medical University, Yinchuan 750001, China | | | Bai Zhoulan | Department of Radiotherapy, Cancer Hospital, the General Hospital of Ningxia Medical University, Yinchuan 750001, China | | | Wang Yanyang | Department of Radiotherapy, Cancer Hospital, the General Hospital of Ningxia Medical University, Yinchuan 750001, China | fdwyy1981@163.com |
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| Abstract:: |
| Objective To observe the effect of ubiquilin 2 gene (UBQLN2) on the radiosensitivity of human esophageal squamous cell carcinoma cells (ESCC) of EC109 and KYSE30, and explore underlying molecular mechanism. Methods siRNA and lentivirus transfection techniques were used to establish UBQLN2-knockdown and UBQLN2-overexpression cell lines. The cells were irradiated with a dose of 4 Gy X-rays. UPLC-Q-TOF-MS technique was used for metabolite difference analysis and KEGG pathway analysis. The results of metabonomics analyses were verified by qRT-PCR assay. The influence of UBQLN2 level on the radiosensitivity of ESCC was confirmed by CCK-8 cell proliferation assay and clone formation assay and further verified by treating the cells with metabolic enzyme inhibitors and exogenous metabolites. Results Compared with irradiation alone, down-regulating UBQLN2 in EC109 and KYSE30 cell lines reduced the cell survival by 32.29% and 16.42% (t=5.35, 4.88, P＜0.05), and reduced the clone formation rate by 11.07% and 7.47% after 4 Gy irradiation, respectively (t=4.18, 5.09, P＜0.05). On the contrary, up-regulating UBQLN2 in EC109 and KYSE30 cell lines increased the survival rate by 14.07% and 10.64% (t=5.88, 4.21, P＜0.05), and increased the clone formation rate by 6.53% and 7.87% after 4 Gy irradiation, respectively (t=8.60, 8.26, P＜0.05). Metabonomics study showed that the purine metabolic pathway was significantly enriched after down-regulating UBQLN2 in EC109 cell. The qRT-PCR experiment showed a positive correlation between the expression level of UBQLN2 and the mRNA level of five purine metabolism enzymes. The viability of irradiated UBQLN2-overexpression cells decreased by 18.28% and 25.58%, respectively (t=7.76, 10.95, P<0.05), and the clone formation rate decreased by 9.33% and 9.93%, respectively (t=5.97, 8.02, P<0.05) after adding mycophenolic acid(MPA). However, the survival rate of cells increased by by 8.28% and 10.74% (t=2.83, 6.20, P<0.05), and the clone formation rate increased by 7.33% and 5.80%, respectively (t=7.16, 5.49, P<0.05), when exogenous supplementation of nucleotides (ATP + GTP) were added. Conclusion The expression level of UBQLN2 was negatively related to the radiosensitivity of ESCC by up-regulating purine metabolism. |
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