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Sevoflurane inhibits lung cancer development by promoting FUS1 transcription via downregulating IRF6  ( SCI-EXPANDED收录)  

文献类型:期刊文献

英文题名:Sevoflurane inhibits lung cancer development by promoting FUS1 transcription via downregulating IRF6

作者:Zhou, Pei[1];Yang, Lei[2];Ma, Xinyu[1,3];Li, Qiuguo[1,3]

第一作者:Zhou, Pei

通信作者:Ma, XY[1];Li, QG[1];Ma, XY[2];Li, QG[2]

机构:[1]Cent South Univ, Xiangya Hosp 2, Dept Anesthesiol, Cent Ren Min Rd 139, Changsha 410011, Hunan, Peoples R China;[2]Gansu Univ Chinese Med, Dept Oncol, 35 Dingxi East Rd, Lanzhou 730000, Gansu, Peoples R China;[3]Hunan Chest Hosp, Dept Surg, 519 Xianjiahu Rd, Changsha 410205, Hunan, Peoples R China

第一机构:Cent South Univ, Xiangya Hosp 2, Dept Anesthesiol, Cent Ren Min Rd 139, Changsha 410011, Hunan, Peoples R China

通信机构:[1]corresponding author), Cent South Univ, Xiangya Hosp 2, Dept Anesthesiol, Cent Ren Min Rd 139, Changsha 410011, Hunan, Peoples R China;[2]corresponding author), Hunan Chest Hosp, Dept Surg, 519 Xianjiahu Rd, Changsha 410205, Hunan, Peoples R China.

年份:2024

卷号:45

期号:8

起止页码:543

外文期刊名:CARCINOGENESIS

收录:;Scopus(收录号:2-s2.0-85201160611);WOS:【SCI-EXPANDED(收录号:WOS:001261598200001)】;

基金:This work is supported by Scientific Research Project of Health Commission of Hunan Province (202204013577).

语种:英文

摘要:Lung cancer is a major contributor to cancer deaths worldwide and is on the rise. Although surgical resection has been widely used as a standard therapy for lung cancer patients, the relapse rate after surgery is high. It is still unclear whether there is a potential drug that can reduce the probability of postsurgical recurrence in lung cancer patients. We used 5 typical lung cancer cell lines as well as 41 lung cancer tissue samples and paracancer tissue samples to investigate the expression levels of interferon regulatory factor 6 (IRF6) and tumor suppressor candidate 2 (TUSC2, also known as FUS1). We also treated lung cancer cells (H322 and A549) with different concentrations of sevoflurane to study its influence on lung cancer cell tumorigenesis. Lentivirus-mediated gain-of-function studies of IRF6 and FUS1 were applied to validate the role of IRF6 and FUS1 in lung cancer. Next, we used short hairpin RNA-mediated loss of function of IRF6 and luciferase, chromatin immunoprecipitation assays to validate the regulatory role of IRF6 on FUS1. Our findings reported that IRF6 was upregulated in lung cancer tissues, while FUS1 was downregulated. Functional assays revealed that sevoflurane inhibits lung cancer development by downregulating IRF6 expression. Luciferase and chromatin immunoprecipitation-quantitative real-time PCR assays uncovered that IRF6 represses FUS1 transcriptional expression in lung cancer cells. We have shown that sevoflurane prevents lung cancer development by downregulating IRF6 to stimulate FUS1 transcription, indicating that sevoflurane can be used as the potential anesthetic drug in surgical resection to reduce postoperative tumor relapse in lung cancer patients. Sevoflurane activated FUS1 transcription by downregulating IRF6, and inhibited the proliferation, migration, and invasion of lung cancer. Graphical Abstract

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