Deng Yanxi, Wang Fang, Wu Xinhui, Du Kangming, Yang Qing, Xia Ting
Clinical Laboratory, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China.
Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China.
Front Pharmacol. 2023 Mar 31;14:1131610. doi: 10.3389/fphar.2023.1131610. eCollection 2023.
Sunitinib is the main target drug for clear cell renal cell carcinoma. However, the effect of sunitinib is often limited by acquired drug resistance. The open-accessed data used in this study were obtained from different online public databases, which were analyzed using the R software. The RNA level of specific genes was detected using quantitative Real-Time PCR. Sunitinib-resistant cell lines were constructed based on protocol get from the previous study. Colony formation and Cell Counting Kit-8 assays were applied to detect cell proliferation ability. In this study, through publicly available data and high-quality analysis, we deeply explored the potential biological mechanisms that affect the resistance of sunitinib. Detailed, data from GSE64052, GSE76068 and The Cancer Genome Atlas were extracted. We identified the IFITM1, IL6, MX2, PCOLCE2, RSAD2 and SLC2A3 were associated with sunitinib resistance. Single-cell analysis, prognosis analysis and m6A regulatory network were conducted to investigate their role. Moreover, the MX2 was selected for further analysis, including its biological role and effect on the ccRCC microenvironment. Interestingly, we noticed that MX2 might be an immune-related gene that could affect the response rate of immunotherapy. Then, experiments validated the overexpression of MX2 in sunitinib-resistance cells. Colony formation assay indicated that the knockdown of MX2 could remarkably inhibit the proliferation ability of 786-O-Res and Caki-1-Res when exposed to sunitinib. In summary, through publicly available data and high-quality analysis, we deeply explored the potential biological mechanisms that affect the resistance of sunitinib. MX2 was selected for further analysis, including its biological role and effect on the ccRCC microenvironment. Finally, experiments were used to validate its role in ccRCC.
舒尼替尼是透明细胞肾细胞癌的主要靶向药物。然而，舒尼替尼的疗效常受获得性耐药的限制。本研究中使用的开放获取数据来自不同的在线公共数据库，并使用R软件进行分析。通过定量实时PCR检测特定基因的RNA水平。基于先前研究的方案构建舒尼替尼耐药细胞系。采用集落形成实验和细胞计数试剂盒-8实验检测细胞增殖能力。在本研究中，通过公开可用的数据和高质量分析，我们深入探究了影响舒尼替尼耐药性的潜在生物学机制。具体而言，提取了来自GSE64052、GSE76068和癌症基因组图谱的数据。我们确定了IFITM1、IL6、MX2、PCOLCE2、RSAD2和SLC2A3与舒尼替尼耐药相关。进行单细胞分析、预后分析和m6A调控网络研究它们的作用。此外，选择MX2进行进一步分析，包括其生物学作用以及对ccRCC微环境的影响。有趣的是，我们注意到MX2可能是一个与免疫相关的基因，可影响免疫治疗的反应率。然后，实验验证了MX2在舒尼替尼耐药细胞中的过表达。集落形成实验表明，敲低MX2可显著抑制786-O-Res和Caki-1-Res在暴露于舒尼替尼时的增殖能力。总之，通过公开可用的数据和高质量分析，我们深入探究了影响舒尼替尼耐药性的潜在生物学机制。选择MX2进行进一步分析，包括其生物学作用以及对ccRCC微环境的影响。最后，通过实验验证其在ccRCC中的作用。
