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Upregulation of Oxidative stress-responsive 1(OXSR1) Predicts Poor Prognosis and Promotes Hepatocellular Carcinoma Progression.
Bioengineered ( IF 4.2 ) Pub Date : 2020-09-03 , DOI: 10.1080/21655979.2020.1814659
Jianhui Chen 1, 2 , Jiangfan Zhou 3 , Haotian Fu 2 , Xiaofeng Ni 1, 2 , Yunfeng Shan 2
Affiliation  

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.



中文翻译:

氧化应激反应 1(OXSR1)的上调预测预后不良并促进肝细胞癌的进展。

许多研究报道氧化应激反应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仍然未知。在目前的研究中,观察到 OXSR1 在 HCC 中的表达异常升高。上调的 OXSR1 与 TNM 分期和分级相关,并被证实为 HCC 患者的独立预后因素。OXSR1 表达的下调在体内和体外实验中有效抑制了 HCC 的增殖、迁移和侵袭。蛋白质印迹和 qRT-PCR 分析表明,突变 p53-R249S 对于调节 HCC 中 OXSR1 的异常升高至关重要。芯片检测表明 p53-R249S 消除了 p53 与 OXSR1 启动子区域的结合并增加了 POL2 的水平,H3Kac 和 H4Kac 位于 OXSR1 的启动子区,从而促进 OXSR1 的转录表达。GSEA 显示在高 OXSR1 表达组中丰富了许多癌症相关通路。此外,通过TIMER平台,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的表达呈正相关。总之,我们的研究表明,OXSR1 上调是 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,HCC 中上调 OXSR1 促进增殖、迁移和侵袭。此外,通过TIMER平台,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的表达呈正相关。总之,我们的研究表明,OXSR1 上调是 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,HCC 中上调 OXSR1 促进增殖、迁移和侵袭。此外,通过TIMER平台,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的表达呈正相关。总之,我们的研究表明,OXSR1 上调是 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,HCC 中上调 OXSR1 促进增殖、迁移和侵袭。

更新日期:2020-09-05
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