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CCDC50 的高表达与 DNA 甲基化相关,与预后不良和肝癌进展相关。

DNA methylation-mediated high expression of CCDC50 correlates with poor prognosis and hepatocellular carcinoma progression.

机构信息

Department of Oncology, Suining Central Hospital, Suining 629000, Sichuan, P.R. China.

Gastrointestinal Surgical Unit, Suining Central Hospital, Suining 629000, Sichuan, P.R. China.

出版信息

Aging (Albany NY). 2023 Aug 7;15(15):7424-7439. doi: 10.18632/aging.204899.

DOI:10.18632/aging.204899
PMID:37552104
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10457044/
Abstract

Hepatocellular carcinoma (HCC) is one of the most common and lethal cancer types worldwide. Recent studies found Coiled-coil domain-containing protein 50 (CCDC50) could regulate the nuclear factor kappa-B and p53 signalling pathways in cancer. Nevertheless, the underlying biological function and potential mechanisms of CCDC50 driving the progression of HCC remain unclear. In this study, we found that CCDC50 was up-regulated in HCC, and its higher expression was associated with adverse clinical outcomes and poor clinical characteristics. The results of the Cox regression analysis revealed that CCDC50 was an independent factor for the prognosis of HCC. Meanwhile, we also established a nomogram based on CCDC50 to predict the 1-, 3-, or 5-year survival in HCC patients. Furthermore, we found that DNA hypomethylation results in its overexpression in HCC. In addition, functional annotation confirmed that CCDC50 was mainly involved in the neuroactive ligand-receptor interaction and protein digestion and absorption. Importantly, we found that CCDC50 was highly expressed in HCC cell lines. Depletion of CCDC50 significantly inhibits HCC cell proliferation and migration abilities. This is the first study to identify CCDC50 as a new potential prognostic biomarker and characterize the functional roles of CCDC50 in the progression of HCC, and provides a novel potential diagnostic and therapeutic biomarker for HCC in the future.

摘要

肝细胞癌 (HCC) 是全球最常见和最致命的癌症类型之一。最近的研究发现卷曲螺旋结构域蛋白 50 (CCDC50) 可以在癌症中调节核因子 kappa-B 和 p53 信号通路。然而,CCDC50 驱动 HCC 进展的潜在生物学功能和潜在机制仍不清楚。在这项研究中,我们发现 CCDC50 在 HCC 中上调,其高表达与不良临床结局和较差的临床特征相关。Cox 回归分析结果表明,CCDC50 是 HCC 预后的独立因素。同时,我们还基于 CCDC50 建立了一个列线图,以预测 HCC 患者的 1、3 或 5 年生存率。此外,我们发现 DNA 低甲基化导致其在 HCC 中过表达。此外,功能注释证实 CCDC50 主要参与神经活性配体-受体相互作用和蛋白质消化吸收。重要的是,我们发现 CCDC50 在 HCC 细胞系中高表达。CCDC50 的缺失显著抑制 HCC 细胞的增殖和迁移能力。这是首次将 CCDC50 鉴定为新的潜在预后生物标志物,并描述了 CCDC50 在 HCC 进展中的功能作用,为 HCC 的未来提供了一种新的潜在诊断和治疗生物标志物。

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PCDH20 inhibits esophageal squamous cell carcinoma proliferation and migration by suppression of the mitogen-activated protein kinase 9/AKT/β-catenin pathway.
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