| 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. |
| MicroRNA30a-5p对裸鼠肺癌皮下移植瘤放射增敏作用的研究 |
| Radiosensitization by microRNA30a-5p in a nude mouse model with subcutaneous lung-cancer xenograft |
| Received:November 15, 2021 Revised:August 03, 2022 |
| DOI：10.1007/s10330-021-0534-4 |
| 中文关键词: Mir-30a-5p; 移植瘤; 放射敏感性; ATM |
| 英文关键词: Mir-30a-5p; subcutaneous xenografts; radiosensitization; ATM |
| 基金项目:肿瘤外泌体miRNA调控Treg细胞在食管鳞癌放射抗拒中的作用及机制 |
| 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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| 中文摘要: |
| 目的：观察mir-30a-5p对裸鼠肺癌皮下移植瘤的放射增敏作用，并探讨其可能机制。方法：通过慢病毒转染构建mir-30a-5p稳定表达或下调及
阴性对照的A549细胞系。应用慢病毒稳转细胞系构建裸鼠肺癌皮下移植模型。每组随机分为照射组和非照射组。成瘤后，照射组给予10Gy/5f/2Gy的4 MV-X射线照射。观察移植瘤生长情况、瘤重，通过免疫组织化学法和Western blotting检测放射增敏相关蛋白的表达，探索mir-30a-5p的体内放射增敏作用及其可能的机制。结果：Lenti-mir-30a-5p组mir-30a-5p的表达高于Lenti-GFP组，而Lenti-inhibitor组，其表达低于Lenti-mir-30a-5p组(均为P<0.05)。照射组和Lenti-mir-30a-5p裸鼠肺癌皮下移植瘤生长缓慢，肿瘤较轻，抑瘤率高于未照射组和Lenti-GFP组。而Lenti-inhibitor组结果相反。免疫组化和Western blotting结果均显示，Lenti-mir-30a-5p照射组ATM蛋白表达较Lenti-GFP组降低，Lenti-mir-30a-5p组ATM蛋白表达升高，Lenti-mir-30a-5p组ATM蛋白表达也升高。未照射组ATMs1981磷酸化水平较低，照射后其磷酸化水平显著升高(P<0.05)。照射后Lenti-mir-30a-5p组ATMs1981磷酸化水平低于Lenti-mir-30a-5p组，Lenti-inhibitor组其磷酸化水平高于Lenti-GFP组(P<0.05)。结论：Mir-30a-5p可通过参与抑制ATM磷酸化激活化来增加裸鼠肺癌皮下移植瘤的放射敏感性。 |
| 英文摘要: |
| 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 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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