| 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 Name | Affiliation | E-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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