Zhou Pei, Yang Lei, Ma Xinyu, Li Qiuguo
Department of Anesthesiology, The Second Xiangya Hospital, Central South University, Central Ren-Min Road, No. 139, Changsha City, Hunan Province 410011, People's Republic of China.
Department of Oncology, Gansu University of Chinese Medicine, No. 35 Dingxi East Road, Chengguan District, Lanzhou City, Gansu Province 730000, People's Republic of China.
Carcinogenesis. 2024 Aug 12;45(8):543-555. doi: 10.1093/carcin/bgae034.
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.
肺癌是全球癌症死亡的主要原因，且呈上升趋势。尽管手术切除已被广泛用作肺癌患者的标准治疗方法，但术后复发率很高。目前仍不清楚是否有一种潜在药物可以降低肺癌患者术后复发的概率。我们使用了5种典型的肺癌细胞系以及41个肺癌组织样本和癌旁组织样本，来研究干扰素调节因子6（IRF6）和肿瘤抑制候选基因2（TUSC2，也称为FUS1）的表达水平。我们还用不同浓度的七氟醚处理肺癌细胞（H322和A549），以研究其对肺癌细胞肿瘤发生的影响。应用慢病毒介导的IRF6和FUS1功能获得性研究来验证IRF6和FUS1在肺癌中的作用。接下来，我们使用短发夹RNA介导的IRF6功能丧失以及荧光素酶、染色质免疫沉淀试验来验证IRF6对FUS1的调节作用。我们的研究结果表明，IRF6在肺癌组织中上调，而FUS1下调。功能试验表明，七氟醚通过下调IRF6表达来抑制肺癌发展。荧光素酶和染色质免疫沉淀-定量实时PCR试验发现，IRF6在肺癌细胞中抑制FUS1的转录表达。我们已经表明，七氟醚通过下调IRF6来刺激FUS1转录，从而预防肺癌发展，这表明七氟醚可作为手术切除中的潜在麻醉药物，以降低肺癌患者术后肿瘤复发率。
