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通过 / 途径导致口腔癌细胞的 DNA 损伤和促进细胞增殖。

Caused DNA Damage and Promoted Cell Proliferation by the / Pathway in Oral Cancer Cells.

机构信息

Department of Periodontics, School of Stomatology, China Medical University, Shenyang, Liaoning, China.

出版信息

DNA Cell Biol. 2020 Jan;39(1):144-151. doi: 10.1089/dna.2019.5064. Epub 2019 Nov 25.

DOI:10.1089/dna.2019.5064
PMID:31765243
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6978777/
Abstract

Bacterial infection influences genomic stability and integrity by causing DNA damage, which increases the possibility of tumor initiation and development. We aimed to investigate whether , one of the periodontal pathogens, promoted oral squamous cell carcinoma (OSCC) by causing DNA double-strand break (DSB). Tca8113 tongue squamous cell carcinoma cells were infected with . The expression of γH2AX was detected by western blots and immunofluorescence. The proliferation and cell cycle alterations were tested by CCK8 and flow cytometry, respectively. The expression levels of Ku70, p53, and p27 were evaluated by quantitative real-time polymerase chain reaction and western blots. A plasmid was used for the overexpression of Ku70 to verify the possible relationship between Ku70 and p53. We confirmed the presence of DSBs in the response to by detecting the expression of γH2AX. The cell proliferation ability was increased with an accelerated cell cycle while the expression of p27 was decreased. Meanwhile, the expression of Ku70 and wild p53 was downregulated. When Ku70 was overexpressed, the expression of wild p53 in response to infection was upregulated and cell proliferation was accordingly inhibited. We concluded that infection promoted the proliferation ability of Tca8113 by causing DNA damage via the Ku70/p53 pathway.

摘要

细菌感染通过引起 DNA 损伤影响基因组稳定性和完整性,从而增加肿瘤起始和发展的可能性。我们旨在研究牙周病病原体之一 是否通过引起 DNA 双链断裂 (DSB) 促进口腔鳞状细胞癌 (OSCC)。用 感染 Tca8113 舌鳞癌细胞。通过 Western blot 和免疫荧光检测 γH2AX 的表达。通过 CCK8 和流式细胞术分别检测细胞增殖和细胞周期改变。通过定量实时聚合酶链反应和 Western blot 评估 Ku70、p53 和 p27 的表达水平。使用质粒过表达 Ku70 来验证 Ku70 和 p53 之间可能存在的关系。通过检测 γH2AX 的表达,我们证实了对 的反应中存在 DSB。细胞增殖能力增加,细胞周期加速,而 p27 的表达减少。同时,Ku70 和野生型 p53 的表达下调。当 Ku70 过表达时,野生型 p53 在 感染反应中的表达上调,细胞增殖相应受到抑制。我们得出结论, 感染通过 Ku70/p53 通路引起 DNA 损伤,从而促进 Tca8113 的增殖能力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77b4/6978777/865d5b0c74d3/dna.2019.5064_figure4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77b4/6978777/b0848a96e9bc/dna.2019.5064_figure1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77b4/6978777/806c6b54fc68/dna.2019.5064_figure2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77b4/6978777/77d84ca15bbe/dna.2019.5064_figure3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77b4/6978777/865d5b0c74d3/dna.2019.5064_figure4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77b4/6978777/b0848a96e9bc/dna.2019.5064_figure1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77b4/6978777/806c6b54fc68/dna.2019.5064_figure2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77b4/6978777/77d84ca15bbe/dna.2019.5064_figure3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77b4/6978777/865d5b0c74d3/dna.2019.5064_figure4.jpg

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