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达沙替尼治疗放射性皮肤溃疡的作用靶点及信号机制。

Therapeutic targets and signaling mechanisms of dasatinib activity against radiation skin ulcer.

机构信息

Department of Plastic and Burn Surgery, The Second Affiliated Hospital of Chengdu Medical College (China National Nuclear Corporation 416 Hospital), Chengdu, China.

Department of Cosmetic Plastic and Burn Surgery, The First Affiliated Hospital of Chengdu Medical College, Chengdu, China.

出版信息

Front Public Health. 2022 Nov 30;10:1031038. doi: 10.3389/fpubh.2022.1031038. eCollection 2022.

Abstract

OBJECTIVE

To reveal the potential targets and signaling pathways of dasatinib in the treatment of radiation ulcers through network pharmacology and molecular docking technology.

METHODS

Pathological targets of radiation ulcers were screened using GeneCards database. At the same time, the pharmacological targets of dasatinib were obtained through SwissTargetPrediction (STP), Binding DB and Drugbank databases. Subsequently, the potential targets of dasatinib for anti-radiation ulcers were obtained after intersection by Venn diagram. Next, a protein-protein interaction (PPI) network was constructed through the STRING database and core targets were screened. Finally, the identified core targets were subjected to GO and KEGG enrichment analysis, co-expression network analysis, and molecular docking technology to verify the reliability of the core targets.

RESULTS

A total of 76 potential targets for anti-radiation ulcer with dasatinib were obtained, and 6 core targets were screened, including EGFR, ERBB2, FYN, JAK2, KIT, and SRC. These genes were mainly enriched in Adherens junction, EGFR tyrosine kinase inhibitor resistance, Focal adhesion, Bladder cancer and PI3K-Akt signaling pathway. Molecular docking results showed that dasatinib binds well to the core target.

CONCLUSION

Dasatinib may play a role in the treatment of radiation ulcers by regulating EGFR, ERBB2, FYN, JAK2, KIT, and SRC. These core targets may provide new insights for follow-up studies of radiation ulcers.

摘要

目的

通过网络药理学和分子对接技术揭示达沙替尼治疗放射性溃疡的潜在靶点及信号通路。

方法

利用基因卡片数据库筛选放射性溃疡的病理靶点。同时,通过瑞士靶向预测(STP)、结合数据库和药物数据库获得达沙替尼的药理靶点。然后,通过韦恩图交集获得达沙替尼治疗放射性溃疡的潜在靶点。接下来,通过 STRING 数据库构建蛋白质-蛋白质相互作用(PPI)网络,并筛选核心靶点。最后,对鉴定的核心靶点进行 GO 和 KEGG 富集分析、共表达网络分析和分子对接技术,验证核心靶点的可靠性。

结果

共获得 76 个达沙替尼治疗放射性溃疡的潜在靶点,筛选出 6 个核心靶点,包括 EGFR、ERBB2、FYN、JAK2、KIT 和 SRC。这些基因主要富集在粘着连接、表皮生长因子受体酪氨酸激酶抑制剂耐药、粘着斑、膀胱癌和 PI3K-Akt 信号通路。分子对接结果表明,达沙替尼与核心靶点结合良好。

结论

达沙替尼可能通过调节 EGFR、ERBB2、FYN、JAK2、KIT 和 SRC 发挥治疗放射性溃疡的作用。这些核心靶点可能为放射性溃疡的后续研究提供新的思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be61/9749824/c88dbb1e9d3a/fpubh-10-1031038-g0001.jpg

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