Knockdown Of TRIM31 Enhances Colorectal Cancer Radiosensitivity By Inducing DNA Damage And Activating Apoptosis

Knockdown Of TRIM31 Enhances Colorectal Cancer Radiosensitivity By Inducing DNA Damage And Activating Apoptosis
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TRIM31 的敲低通过诱导 DNA 损伤和激活细胞凋亡来增强结直肠癌的放射敏感性

DOI:
10.2147/ott.s215769
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发表时间:
2019-10
影响因子:
4
通讯作者:
Zhang Zhen
Zhang Zhen
中科院分区:
医学3区
文献类型:
--
作者:
Zhang Hui;Deng Yun;Liang Liping;Shen Lijun;Zhu Ji;Wang Yaqi;Zhang Jing;Zhang Zhen

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目的预测放射敏感性的生物标志物是个体化放射治疗的基础。我们对直肠癌患者术前放疗反应良好和反应不良的患者进行了微阵列分析,发现含三重基序蛋白31(TRIM 31)表达较低的患者表现出更好的反应。在这项研究中,我们通过敲低结直肠癌细胞中的TRIM 31来证实TRIM 31对放射敏感性的影响。方法和材料使用TRIM 31稳定敲低的人结直肠癌细胞系HT-29和SW 480进行分析。我们研究了TRIM 31基因敲减细胞在辐射后DNA损伤水平及相关蛋白的变化。流式细胞仪检测照射后细胞凋亡、细胞周期和活性氧(ROS)水平。通过克隆测定测量细胞存活。Western blotting检测DNA损伤相关蛋白。结果TRIM 31基因敲低的细胞凋亡率和ROS水平升高,存活率降低。TRIM 31基因敲低细胞中DNA损伤蛋白磷酸化共济失调-毛细血管扩张突变(P-ATM)、DNA蛋白激酶(DNA-PKs)和γ-H2 AX的表达水平较高。结论TRIM 31基因敲低可增加大肠癌细胞的DNA损伤和放射敏感性。
Purpose Biomarkers that predict radiosensitivity are essential for personalized radiotherapy. We performed microarray analysis for rectal cancer patients between those with good response and poor response to preoperative radiotherapy and found that patients with lower expression of tripartite motif-containing protein 31 (TRIM31) showed a better response. In this study, we confirmed the effects of TRIM31 on radiosensitivity by knockdown of TRIM31 in colorectal cancer cells. Methods and materials Human colorectal cancer cell lines HT-29 and SW480, which are TRIM31 stably knocked-down, were used for analysis. We studied the level of DNA damage and the change of relative proteins after irradiation in TRIM31-knockdown cells. Flow cytometry was used to test for apoptosis, cell cycle stage, and reactive oxygen species (ROS) levels after irradiation. Cell survival was measured by cloning assay. Proteins related to DNA damage were evaluated by Western blotting. Results The percentage of apoptotic cells and the levels of ROS were elevated, and the survival fraction was reduced in TRIM31-knockdown cells. The expression levels of the DNA damage proteins phosphorylated ataxia-telangiectasia mutation (P-ATM), DNA protein kinases (DNA-PKs), and γ-H2AX were higher in TRIM31-knockdown cells. Conclusion Knockdown of TRIM31 increases DNA damage and radiosensitivity in colorectal cancer cells.
DOI: 10.1038/nri2413
发表时间: 2008-11
期刊: Nature reviews. Immunology
影响因子: --
作者:
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通讯作者: Morse HC 3rd
DOI: 10.1891/9780826121646.0002
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DOI: 10.7150/thno.23259
发表时间: 2018
期刊: Theranostics
影响因子: 12.4
作者:
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DOI: 10.1200/jco.2011.29.15_suppl.3516
发表时间: 2011
期刊: Journal of clinical oncology : official journal of the American Society of Clinical Oncology
影响因子: --
作者:
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DOI: 10.1007/s13277-014-1763-x
发表时间: 2014-06-01
期刊: TUMOR BIOLOGY
影响因子: --
作者:
Li, Hui;Zhang, Yi;He, Ping
通讯作者: He, Ping