Radiosensitization by microRNA30a-5p in a nude mouse model with subcutaneous lung-cancer xenograft  

作　　者：Yuyan Guo Yingtao Cui Xing Bao Yue Ke Hongtao Ren Jiyuan Pan Liping Song Hongbing Ma 

机构地区：[1]Department of Radiation Oncology,the Second Affiliated Hospital of Xi’an Jiaotong University,Xi’an 710004,China [2]Department of Radiation Oncology,the First Affiliated Hospital of Xi’an Jiaotong University,Xi’an 710061,China

出　　处：《Oncology and Translational Medicine》2022年第4期155-164,共10页肿瘤学与转化医学（英文版）

基　　金：supported by the National Science Fund Project (No. 81872471);the National Natural Science Foundation of China and the Science Foundation of the Second Affiliated Hospital of Xi’an Jiaotong University (No. YJ(QN)202025)

摘　　要：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 lung-cancer 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.

关 键 词：Mir-30a-5p subcutaneous xenografts RADIOSENSITIZATION ATM 

分 类 号：R734.2[医药卫生—肿瘤]