Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University , Wenzhou, Zhejiang Province, People's Republic of China.
Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University , Wenzhou, Zhejiang Province, People's Republic of China.
Bioengineered. 2020 Dec;11(1):958-971. doi: 10.1080/21655979.2020.1814659.
Many studies reported that Oxidative stress-responsive 1(OXSR1) is closely related to the malignant progression of several malignancies. Nevertheless, the expression pattern and function of OXSR1 in HCC remains unknown. In present research, it was observed that the expression of OXSR1 was abnormally elevated in HCC. Upregulated OXSR1 was associated with TNM stage, and grade and was confirmed as an independent prognostic factor in HCC patients. The downregulation of OXSR1 expression effectively repressed the proliferation, migration and invasion of HCC in vivo and in vitro experiments. Western blot and qRT-PCR analysis demonstrated that mutant p53-R249S was critical for regulating the aberrant elevation of OXSR1 in HCC. Chip assay indicated that p53-R249S abrogated the binding of p53 to the OXSR1 promoter region and increased the level of POL2, H3Kac and H4Kac in the promoter region of the OXSR1, thus promoting the transcriptional expression of OXSR1. GSEA revealed that numerous cancer-related pathways were enriched in the high OXSR1 expression group. Furthermore, the expression level of OXSR1 was positively correlated with the infiltration levels of tumor infiltrating immune cells (TIICs) and PD-L1 expression in HCC by TIMER platform. In summary, our study revealed that upregulated OXSR1 was a determinant of prognosis and immune infiltration in HCC. The expression of OXSR1 was released by p53-R249S mutant, and upregulated OXSR1 in HCC promoted proliferation, migration and invasion.
许多研究表明，氧化应激反应 1（OXSR1）与多种恶性肿瘤的恶性进展密切相关。然而，OXSR1 在 HCC 中的表达模式和功能尚不清楚。在本研究中，观察到 OXSR1 在 HCC 中的表达异常升高。上调的 OXSR1 与 TNM 分期、分级相关，并被确认为 HCC 患者的独立预后因素。下调 OXSR1 表达可有效抑制 HCC 的体内和体外增殖、迁移和侵袭。Western blot 和 qRT-PCR 分析表明，突变型 p53-R249S 是调节 HCC 中 OXSR1 异常升高的关键因素。芯片分析表明，p53-R249S 削弱了 p53 与 OXSR1 启动子区域的结合，并增加了 OXSR1 启动子区域 POL2、H3Kac 和 H4Kac 的水平，从而促进了 OXSR1 的转录表达。GSEA 显示，在高 OXSR1 表达组中富集了许多与癌症相关的途径。此外，通过 TIMER 平台发现，OXSR1 的表达水平与 HCC 中肿瘤浸润免疫细胞（TIICs）的浸润水平和 PD-L1 表达呈正相关。总之，我们的研究表明，上调的 OXSR1 是 HCC 预后和免疫浸润的决定因素。OXSR1 的表达由 p53-R249S 突变体释放，上调的 OXSR1 在 HCC 中促进增殖、迁移和侵袭。
