Yuyan Guo,Yingtao Cui,Xing Bao,Yue Ke,Hongtao Ren,Jiyuan Pan,Liping Song,Hongbing Ma. Radiosensitization by microRNA30a-5p in a nude mouse model with subcutaneous lung-cancer xenograft. Oncol Transl Med, 2022, 8: 155-164.
Radiosensitization by microRNA30a-5p in a nude mouse model with subcutaneous lung-cancer xenograft
Received:November 15, 2021  Revised:August 03, 2022
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KeyWord:Mir-30a-5p; subcutaneous xenografts; radiosensitization; ATM
Author NameAffiliationE-mail
Yuyan Guo Department of Radiation Oncology, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an , China guoyuyan120@163.com 
Yingtao Cui Department of Radiation Oncology, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an , China  
Xing Bao Department of Radiation Oncology, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an , China  
Yue Ke Department of Radiation Oncology, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an , China  
Hongtao Ren Department of Radiation Oncology, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an , China  
Jiyuan Pan Department of Radiation Oncology, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an , China  
Liping Song Department of Radiation Oncology, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an , China  
Hongbing Ma Department of Radiation Oncology, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an , China mhbxian@126.com 
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Abstract:
      Objective: We aimed to observe the radiosensitization effect of mir-30a-5p in a nude mouse model with subcutaneous lung-cancer xenograft and to explore the underlying mechanism. Methods: A549 cell lines with either stable upregulation or downregulation of mir-30a-5p, and their negative control, were transfected with lentivirus vectors. These cell lines were used to establish a nude mouse model with subcutaneous lung-cancer xenograft. Each group was randomly divided into irradiated and non-irradiated groups. The radiosensitization effect of mir-30a-5p in vivo was studied by observing xenograft growth trends and tumor weight. The mechanisms involved in this radiosensitization were investigated by detecting expressed radiosensitization-related proteins, using immunohistochemistry and Western blotting. Results: The expression level of mir-30a-5p in the lenti-mir-30a-5p group was higher than that in the negative control (lenti-GFP) group and lower in the lenti-inhibitor group (P < 0.05). Subcutaneous lungcancer xenografts in the irradiation group and lenti-mir-30a-5p increased in size slowly; tumors were lighter and tumor inhibition rates were higher than those in the non-irradiation and lenti-GFP groups. In contrast, the opposite of these effects was observed in the lenti-inhibitor group. Immunohistochemistry and Western blotting indicated that ATM protein expression level was lower in the lenti-mir-30a-5p group, with or without irradiation, compared to that in the lenti-GFP group. ATM protein levels were higher in the lenti-inhibitor groups. The phosphorylation level of ATM at residue 1981 was low in the groups without irradiation and increased significantly after irradiation (P < 0.05). Moreover, the phosphorylation level was lower in the lenti-mir-30a-5p group and higher in the lenti-inhibitor group than that in the lenti-GFP group after irradiation (P < 0.05). Conclusion: Mir-30a-5p enhanced the radiosensitivity of nude mice with subcutaneous lung-cancer xenografts by inhibiting ATM phosphorylation.
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