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基于蛋白质-蛋白质相互作用网络的槲皮素治疗肺鳞状细胞癌的机制

The Mechanism of Quercetin in the Treatment of Lung Squamous Cell Carcinoma Based on a Protein-Protein Interaction Network.

作者信息

Lu Yiping, Zhang Wenfeng, Li Huayao, Liu Cun, Gao Dandan, Zhuang Jing, Liu Ruijuan, Wu Jibiao, Sun Changgang

机构信息

Institute of Integrated Medicine, Medicine College, Qingdao University, Qingdao, Shandong 266071, China.

College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250014, China.

出版信息

Evid Based Complement Alternat Med. 2022 Dec 27;2022:9985160. doi: 10.1155/2022/9985160. eCollection 2022.

DOI:10.1155/2022/9985160
PMID:36605099
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9810414/
Abstract

BACKGROUND

Lung squamous cell carcinoma (LUSC) is characterized by poor prognosis and obvious limitations of therapeutic methods. The molecular target and mechanism of quercetin (QR), a natural anticancer product with extensive pharmacological activities, on lung squamous cell carcinoma is still unclear.

METHOD

The effects of QR on LUSC were examined using cell proliferation, migration, and invasion tests. Key target genes were screened using The Cancer Genome Atlas (TCGA) database, Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) database, STRING website, topology, and prognosis analysis, molecular docking, and other bioinformatics methods for further analysis. Finally, the effects of QR on the expression of key targets in LUSC cells were detected using a cell cycle assay and western blotting.

RESULTS

Our study demonstrates that QR not only inhibits the proliferation of LUSC but also affects the invasion and metastasis of LUSC. After downloading and analyzing the TCGA database, 2150 differentially expressed genes were identified. PLK1, CDC20, and BUB1B were identified using enrichment analysis, topological network analysis, cluster analysis, and molecular docking screening. Subsequent experiments showed that QR could interfere with the cell cycle and downregulate the expression of the target gene PLK1 at the protein level.

CONCLUSIONS

We found that QR not only inhibits the proliferation, migration, and invasion but also blocks the cell cycle progression of LUSC. QR downregulated the expression of the LUSC target gene PLK1 at the protein level.

摘要

背景

肺鳞状细胞癌(LUSC)预后较差,治疗方法存在明显局限性。槲皮素(QR)是一种具有广泛药理活性的天然抗癌产物,其对肺鳞状细胞癌的分子靶点和机制尚不清楚。

方法

通过细胞增殖、迁移和侵袭试验检测QR对LUSC的作用。利用癌症基因组图谱(TCGA)数据库、基因本体论(GO)/京都基因与基因组百科全书(KEGG)数据库、STRING网站、拓扑学和预后分析、分子对接等生物信息学方法筛选关键靶基因,进行进一步分析。最后,通过细胞周期检测和蛋白质印迹法检测QR对LUSC细胞中关键靶点表达的影响。

结果

我们的研究表明,QR不仅抑制LUSC的增殖,还影响LUSC的侵袭和转移。下载并分析TCGA数据库后,鉴定出2150个差异表达基因。通过富集分析、拓扑网络分析、聚类分析和分子对接筛选鉴定出PLK1、CDC20和BUB1B。后续实验表明,QR可干扰细胞周期,并在蛋白质水平下调靶基因PLK1的表达。

结论

我们发现QR不仅抑制LUSC的增殖、迁移和侵袭,还阻断LUSC的细胞周期进程。QR在蛋白质水平下调LUSC靶基因PLK1的表达。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3aed/9810414/64a6ddfcd090/ECAM2022-9985160.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3aed/9810414/6aaab9bf9e52/ECAM2022-9985160.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3aed/9810414/9fb486008af2/ECAM2022-9985160.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3aed/9810414/26bbdba91248/ECAM2022-9985160.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3aed/9810414/898c6bca9c00/ECAM2022-9985160.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3aed/9810414/64a6ddfcd090/ECAM2022-9985160.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3aed/9810414/6aaab9bf9e52/ECAM2022-9985160.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3aed/9810414/9fb486008af2/ECAM2022-9985160.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3aed/9810414/26bbdba91248/ECAM2022-9985160.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3aed/9810414/898c6bca9c00/ECAM2022-9985160.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3aed/9810414/64a6ddfcd090/ECAM2022-9985160.005.jpg

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