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On-line Access: 2021-11-16

Received: 2021-02-24

Revision Accepted: 2021-05-24

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Citations:  Bibtex RefMan EndNote GB/T7714

 ORCID:

Lisha ZHOU

https://orcid.org/0000-0001-7038-4984

Yingying ZHU

https://orcid.org/0000-0002-2543-4476

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Journal of Zhejiang University SCIENCE B 2021 Vol.22 No.11 P.959-965

http://doi.org/10.1631/jzus.B2100170


NEDD8-conjugating enzyme E2 UBE2F confers radiation resistance by protecting lung cancer cells from apoptosis


Author(s):  Lisha ZHOU, Changsheng DONG, Zhuoming XU, Xinran WANG, Luyi ZHANG, Siyuan CHEN, Jiahao CHEN, Yingying ZHU

Affiliation(s):  Department of Basic Medicine, Medical College, Taizhou University, Taizhou 318000, China; more

Corresponding email(s):   lishazhou@tzc.edu.cn, zhuyingying1988@tzc.edu.cn

Key Words:  UBE2F, oxidative stress, Radiosensitization, Apoptosis, Lung cancer


Lisha ZHOU, Changsheng DONG, Zhuoming XU, Xinran WANG, Luyi ZHANG, Siyuan CHEN, Jiahao CHEN, Yingying ZHU. NEDD8-conjugating enzyme E2 UBE2F confers radiation resistance by protecting lung cancer cells from apoptosis[J]. Journal of Zhejiang University Science B, 2021, 22(11): 959-965.

@article{title="NEDD8-conjugating enzyme E2 UBE2F confers radiation resistance by protecting lung cancer cells from apoptosis",
author="Lisha ZHOU, Changsheng DONG, Zhuoming XU, Xinran WANG, Luyi ZHANG, Siyuan CHEN, Jiahao CHEN, Yingying ZHU",
journal="Journal of Zhejiang University Science B",
volume="22",
number="11",
pages="959-965",
year="2021",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B2100170"
}

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%T NEDD8-conjugating enzyme E2 UBE2F confers radiation resistance by protecting lung cancer cells from apoptosis
%A Lisha ZHOU
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%A Zhuoming XU
%A Xinran WANG
%A Luyi ZHANG
%A Siyuan CHEN
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%A Yingying ZHU
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T1 - NEDD8-conjugating enzyme E2 UBE2F confers radiation resistance by protecting lung cancer cells from apoptosis
A1 - Lisha ZHOU
A1 - Changsheng DONG
A1 - Zhuoming XU
A1 - Xinran WANG
A1 - Luyi ZHANG
A1 - Siyuan CHEN
A1 - Jiahao CHEN
A1 - Yingying ZHU
J0 - Journal of Zhejiang University Science B
VL - 22
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SP - 959
EP - 965
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PB - Zhejiang University Press & Springer
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DOI - 10.1631/jzus.B2100170


Abstract: 
lung cancer, which is exacerbated by environmental pollution and tobacco use, has become the most common cause of cancer-related deaths worldwide, with a five-year overall survival rate of only 19% (Siegel et al., 2020; Yang et al., 2020; Yu and Li, 2020). Nearly 85% of lung cancers are non-small cell lung cancers, of which lung adenocarcinoma is the most common subtype accounting for 50% of non-small cell lung cancer cases. At present, radiotherapy is the primary therapeutic modality for lung cancer at different stages, with significant prolongation of survival time (Hirsch et al., 2017; Bai et al., 2019; Shi et al., 2020). Irradiation can generate reactive oxygen species (ROS) through the radiolysis reaction of water and oxygen, cause DNA damage and oxidative stress, and subsequently result in cancer cell death (Kim et al., 2019). Nevertheless, radioresistance seriously hinders the success of treatment for lung cancer, owing to local recurrence and distant metastasis (Huang et al., 2021). Compared with small cell lung cancer, non-small cell lung cancer shows more tolerance to radiotherapy. Therefore, it is of great importance to decipher key mechanisms of radioresistance and identify effective molecular radiosensitizers to improve patient survival.

NEDD8结合酶(E2)UBE2F抑制肺癌细胞凋亡导致其放疗抵抗

目的:放射治疗是非小细胞肺癌的重要治疗手段之一,而放疗抵抗限制了放疗的疗效,导致患者生存率低。因此,鉴定新型的放射增敏靶标将具有重要的临床实践意义。
创新点:揭示灭活NEDD8结合酶(E2)UBE2F可以诱导凋亡蛋白NOXA介导的细胞凋亡,提高肺癌细胞的放疗敏感性。鉴于UBE2F在肺癌放射增敏治疗中的潜在作用,靶向UBE2F有望成为一种新型有效的肺癌放射增敏策略。
方法:利用免疫印迹检测UBE2F和NOXA的表达情况;用台盼蓝染色法检测放射和双氧水处理后肺癌细胞的存活率;通过裸鼠皮下瘤模型来评估动物体内UBE2F表达对肺癌细胞放疗敏感性的影响。
结论:放射或双氧水等氧化压力处理可以诱导UBE2F表达,而活性氧(ROS)清除剂可完全阻断UBE2F的表达上调。氧化压力诱导的UBE2F高表达促进NOXA降解,抑制细胞凋亡,进而导致肺癌细胞放疗抵抗。而灭活UBE2F可以促进NOXA蛋白积聚,促进细胞凋亡,显著提高肺癌细胞对放疗的敏感性。此外,TCGA癌症数据分析显示UBE2F在人肺腺癌中的过表达导致总体生存率较低,进一步提示UBE2F是潜在的放射增敏靶标。

关键词:UBE2F;氧化应激;放疗增敏;细胞凋亡;肺癌

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