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水苏糖在肝细胞癌中的关键分子靶点鉴定:聚焦于信号转导和转录激活因子3(STAT3)及纤连蛋白1(FN1)

Identification of key molecular targets for stachyose in hepatocellular carcinoma: focus on STAT3 and FN1.

作者信息

Chen Haihua, Wang Xianyou, Ying Jiongcheng, Huang YuQin, Liu Yuxi, Feng Yifu, Fang Binbo

机构信息

Department of Hepatobiliary Surgery, Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University, Linhai, Zhejiang, China.

Department of Surgery, Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University, Linhai, Zhejiang, China.

出版信息

Front Oncol. 2025 Jul 23;15:1576449. doi: 10.3389/fonc.2025.1576449. eCollection 2025.

Abstract

BACKGROUND AND OBJECTIVE

Hepatocellular carcinoma (HCC) ranks among the most prevalent malignancies on a global scale. Stachyose (STA), an oligosaccharide widely present in legumes, has demonstrated various biological activities, including improving gut microbiota, anti-oxidative stress, and anti-tumor proliferation. This study aimed to predict potential targets of STA in HCC treatment and to identify key hub genes.

METHODS

By integrating multiple public databases and bioinformatics tools, we screened 34 candidate targets and constructed STA's action network and PPI network in HCC. Functional enrichment analysis revealed 10 relevant KEGG pathways and key features related to cellular components, molecular functions, and biological processes. Finally, we conducted molecular docking, single gene analysis, and experimental validation on core targets.

RESULTS

Through screening of multiple databases, we identified 34 common targets associated with STA and HCC and subsequently constructed a protein-protein interaction (PPI) network. Through this analysis, we ultimately selected STAT3 and FN1 as core hub genes. Functional and pathway analyses indicated that these targets participate in multiple cancer-related pathways and have significant roles in cellular components, biological processes, and molecular functions. The results indicated a positive correlation between the expression of STAT3 and FN1 with angiogenesis, tumor inflammation, and epithelial-mesenchymal transition (EMT). Molecular docking experiments validated the stable binding capacity between STA and these core genes, and experiments further confirmed that STA could inhibit HCC cell proliferation and migration by downregulating STAT3 and FN1 expression.

CONCLUSION

This study offers a comprehensive exploration of the molecular mechanisms through which STA may treat HCC, identifying STAT3 and FN1 as key targets and validating their clinical relevance and potential for application.

摘要

背景与目的

肝细胞癌(HCC)是全球最常见的恶性肿瘤之一。水苏糖(STA)是一种广泛存在于豆类中的寡糖,已显示出多种生物学活性,包括改善肠道微生物群、抗氧化应激和抗肿瘤增殖。本研究旨在预测STA在HCC治疗中的潜在靶点,并确定关键的枢纽基因。

方法

通过整合多个公共数据库和生物信息学工具,我们筛选了34个候选靶点,并构建了STA在HCC中的作用网络和蛋白质-蛋白质相互作用(PPI)网络。功能富集分析揭示了10条相关的KEGG通路以及与细胞成分、分子功能和生物学过程相关的关键特征。最后,我们对核心靶点进行了分子对接、单基因分析和实验验证。

结果

通过对多个数据库的筛选,我们鉴定出34个与STA和HCC相关的共同靶点,并随后构建了蛋白质-蛋白质相互作用(PPI)网络。通过该分析,我们最终选择STAT3和FN1作为核心枢纽基因。功能和通路分析表明,这些靶点参与多个癌症相关通路,并且在细胞成分、生物学过程和分子功能中具有重要作用。结果表明STAT3和FN1的表达与血管生成、肿瘤炎症和上皮-间质转化(EMT)呈正相关。分子对接实验验证了STA与这些核心基因之间的稳定结合能力,并且实验进一步证实STA可通过下调STAT3和FN1的表达来抑制HCC细胞的增殖和迁移。

结论

本研究全面探索了STA治疗HCC的分子机制,确定STAT3和FN1为关键靶点,并验证了它们的临床相关性和应用潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63cf/12325021/bd10e7f624f7/fonc-15-1576449-g002.jpg

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