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MBD2与肾细胞癌的不良预后和肿瘤进展相关。

MBD2 Correlates with a Poor Prognosis and Tumor Progression in Renal Cell Carcinoma.

作者信息

Li Liantao, Li Na, Liu Nianli, Huo Fuchun, Zheng Junnian

机构信息

Cancer Institute, Xuzhou Medical University, Xuzhou 221000, People's Republic of China.

Center of Clinical Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221000, People's Republic of China.

出版信息

Onco Targets Ther. 2020 Oct 7;13:10001-10012. doi: 10.2147/OTT.S256226. eCollection 2020.

Abstract

PURPOSE

DNA methylation plays an important role in regulating gene expression. Methyl-CpG-binding domain (MBD) proteins recognize and bind to methylated DNA, which mediate gene silencing by the interaction with deacetylases and histone methyltransferases. MBD2 has been reported in various human cancers; however, its clinical implication and potential regulatory role in renal cell carcinoma (RCC) have not been elaborated.

MATERIALS AND METHODS

In the study, we estimated the expression and prognostic value of in RCC cell lines and tissues by Western blotting and immunohistochemistry. The associations of expression and pathological characters and survival in RCC patients were performed using χ2 and Kaplan-Meier survival analysis, respectively. Univariate and multivariable Cox regression analyses suggested the independent predictors in RCC prognosis. The functional role of in RCC progression was assessed by in vitro cell experiments. In addition, we identified the -mediated alterations of protein-related proliferation and EMT markers in RCC cells after overexpression and knockdown.

RESULTS

We found that the protein levels of were upregulated in RCC cells and tissues. High expression was related to TNM stage and predicted poorer survival in RCC. Enforced expression of significantly promoted the proliferation, cycle progress, invasion and migration of RCC cells in vitro. However, downregulating remarkably weakened the above cell functions. Mechanistically, the promotive effect of overexpression may be regulated by its effects on and expression and EMT process.

CONCLUSION

These results indicated that confers an oncogenic function in the malignant progression of RCC. could be served as a meaningful prognostic biomarker and a latent therapeutic target in RCC patients.

摘要

目的

DNA甲基化在调节基因表达中起重要作用。甲基化CpG结合域(MBD)蛋白识别并结合甲基化DNA,通过与去乙酰化酶和组蛋白甲基转移酶相互作用介导基因沉默。MBD2已在多种人类癌症中被报道;然而,其在肾细胞癌(RCC)中的临床意义和潜在调节作用尚未阐明。

材料与方法

在本研究中,我们通过蛋白质免疫印迹法和免疫组织化学评估了MBD2在RCC细胞系和组织中的表达及预后价值。分别使用χ2检验和Kaplan-Meier生存分析来分析RCC患者中MBD2表达与病理特征及生存情况的相关性。单因素和多因素Cox回归分析提示了RCC预后的独立预测因素。通过体外细胞实验评估MBD2在RCC进展中的功能作用。此外,我们在MBD2过表达和敲低后鉴定了RCC细胞中与蛋白质相关的增殖和上皮-间质转化(EMT)标志物的MBD2介导的改变。

结果

我们发现RCC细胞和组织中MBD2的蛋白水平上调。MBD2高表达与TNM分期相关,并预测RCC患者生存较差。在体外,MBD2的强制表达显著促进了RCC细胞的增殖、细胞周期进程、侵袭和迁移。然而,下调MBD2明显削弱了上述细胞功能。机制上,MBD2过表达的促进作用可能受其对E-cadherin和Vimentin表达及EMT过程的影响所调控。

结论

这些结果表明MBD2在RCC的恶性进展中赋予致癌功能。MBD2可作为RCC患者有意义的预后生物标志物和潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/447b/7548338/045aa986a5a2/OTT-13-10001-g0001.jpg

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