FBXO family genes promotes hepatocellular carcinoma via ubiquitination of p53.

IF 2.7 3区 医学 Q3 ONCOLOGY
Qingge Gong, La Zhang, Jiao Guo, Wei Zhao, Baoyong Zhou, Changhong Yang, Ning Jiang
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引用次数: 0

Abstract

FBXO protein family plays an essential role in the ubiquitination process acting as E3 ligases, which may contribute to the progression of cancers. However, the molecular functions of FBXOs in hepatocellular carcinoma (HCC) remain incompletely understood. Here, we investigated the overlapping genes between the FBXOs and differentially expressed genes (DEGs) of HCC identified by utilizing The Cancer Genome Atlas (TCGA) dataset, then, a prognostic model with effective predictive capacity was constructed based on the uni-cox and LASSO regression analyses. To elucidate the underlying mechanism of the FBXO model genes, KEGG analysis was carried out. Drug metabolism-cytochrome P450 and retinol metabolism were revealed as the potential pathway, which Increased the credibility of subsequent drug prediction research. Meanwhile, patients divided by the prognostic model showed a different immune infiltrating status and we also found FBXO model genes may ubiquitinate P53, inducing TP53 more prone to mutations, thereby promoting the occurrence and development of tumors. Consistent with these findings, the result of immunohistochemistry (IHC) validated an elevated expression of these model genes in HCC tissues than in the adjacent tissues. The primary aim of this investigation is to formulate a prognostic model while exploring the underlying mechanisms associated with FBXO genes in HCC. These findings offer initial research perspectives on the involvement of FBXO genes in HCC and contribute to the discovery of dependable biomarkers for the management, prognostication, and early detection of HCC in patients.

FBXO 家族基因通过泛素化 p53 促进肝细胞癌的发生。
FBXO 蛋白家族在泛素化过程中扮演着 E3 连接酶的重要角色,这可能会导致癌症的恶化。然而,FBXOs 在肝细胞癌(HCC)中的分子功能仍不完全清楚。在此,我们利用癌症基因组图谱(TCGA)数据集研究了FBXOs与HCC差异表达基因(DEGs)之间的重叠基因,然后基于uni-cox和LASSO回归分析构建了一个具有有效预测能力的预后模型。为了阐明 FBXO 模型基因的内在机制,研究人员进行了 KEGG 分析。结果显示,药物代谢-细胞色素 P450 和视黄醇代谢是潜在的途径,这增加了后续药物预测研究的可信度。同时,按预后模型划分的患者表现出不同的免疫浸润状态,我们还发现 FBXO 模型基因可能泛素化 P53,诱导 TP53 更易发生突变,从而促进肿瘤的发生和发展。与这些发现相一致,免疫组化(IHC)结果验证了这些模型基因在 HCC 组织中的表达高于邻近组织。这项研究的主要目的是建立一个预后模型,同时探索与 FBXO 基因在 HCC 中相关的潜在机制。这些发现为 FBXO 基因参与 HCC 提供了初步的研究视角,有助于发现可靠的生物标志物,用于 HCC 患者的管理、预后和早期检测。
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来源期刊
CiteScore
4.00
自引率
2.80%
发文量
577
审稿时长
2 months
期刊介绍: The "Journal of Cancer Research and Clinical Oncology" publishes significant and up-to-date articles within the fields of experimental and clinical oncology. The journal, which is chiefly devoted to Original papers, also includes Reviews as well as Editorials and Guest editorials on current, controversial topics. The section Letters to the editors provides a forum for a rapid exchange of comments and information concerning previously published papers and topics of current interest. Meeting reports provide current information on the latest results presented at important congresses. The following fields are covered: carcinogenesis - etiology, mechanisms; molecular biology; recent developments in tumor therapy; general diagnosis; laboratory diagnosis; diagnostic and experimental pathology; oncologic surgery; and epidemiology.
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