生物信息学和系统生物学的综合分析揭示了Girdin与肝细胞癌之间的关联。

Comprehensive analysis of bioinformatics and system biology reveals the association between Girdin and hepatocellular carcinoma.

作者信息

Huang Tengda, Chen Hongying, Pan Hongyuan, Wu Tian, Ren Xiangyi, Qin Liwen, Yuan Kefei, He Fang

机构信息

Division of Liver Surgery, Department of General Surgery and Laboratory of Liver Surgery, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.

Cytology and Molecular Platform, Core Facilities of West China Hospital, Chengdu, China.

出版信息

PLoS One. 2024 Dec 13;19(12):e0315534. doi: 10.1371/journal.pone.0315534. eCollection 2024.

DOI:10.1371/journal.pone.0315534

PMID:39671369

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11642971/

Abstract

INTRODUCTION

Hepatocellular carcinoma is one of the leading causes of cancer-related mortality worldwide. The actin-binding protein Girdin is overexpressed in various tumors, promoting tumorigenesis and progression. However, the exact mechanisms by which Girdin regulates liver cancer remain poorly understood.

METHODS

This study comprehensively analyzed the expression level of Girdin in liver cancer and adjacent tissue, along with the correlation between Girdin expression and the clinical characteristics and prognosis of liver cancer. The analysis integrated data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and Clinical Proteomic Tumor Analysis Consortium (CPTAC) database. Subsequently, Girdin expression was knocked down to elucidate its role in the progression of liver cancer. Transcriptome sequencing was employed to investigate the mechanistic underpinnings of Girdin's regulatory impact on liver cancer. Additionally, the Comparative Toxicogenomics Database (CTD) was utilized to identify potential drugs or molecules for liver cancer treatment.

RESULTS

The findings revealed elevated Girdin expression in liver cancer tissues, and heightened Girdin expression correlating with adverse clinical features and prognosis. Silencing of Girdin markedly impeded the proliferation and migration of hepatocellular carcinoma cells. Moreover, transcriptome sequencing demonstrated that silencing Girdin led to differential expression of 176 genes and inhibition of the PI3K/Akt signaling pathway, as well as its upstream pathways-Cytokine-cytokine receptor interaction and Chemokine signaling pathway. Ultimately, we propose that Imatinib Mesylate, Orantinib, Resveratrol, Sorafenib, and Curcumin may interact with Girdin, potentially contributing to the treatment of liver cancer.

CONCLUSION

This study reveals the association between Girdin and hepatocellular carcinoma, providing novel clues for future research and treatment of hepatocellular carcinoma.

摘要

引言

肝细胞癌是全球癌症相关死亡的主要原因之一。肌动蛋白结合蛋白Girdin在多种肿瘤中过度表达，促进肿瘤发生和进展。然而，Girdin调节肝癌的确切机制仍知之甚少。

方法

本研究综合分析了Girdin在肝癌组织和癌旁组织中的表达水平，以及Girdin表达与肝癌临床特征和预后的相关性。该分析整合了来自癌症基因组图谱（TCGA）、基因表达综合数据库（GEO）和临床蛋白质组肿瘤分析联盟（CPTAC）数据库的数据。随后，敲低Girdin的表达以阐明其在肝癌进展中的作用。采用转录组测序来研究Girdin对肝癌调节作用的机制基础。此外，利用比较毒理基因组学数据库（CTD）来识别潜在的肝癌治疗药物或分子。

结果

研究结果显示肝癌组织中Girdin表达升高，且Girdin表达升高与不良临床特征和预后相关。敲低Girdin明显阻碍了肝癌细胞的增殖和迁移。此外，转录组测序表明，敲低Girdin导致176个基因差异表达，并抑制PI3K/Akt信号通路及其上游通路——细胞因子-细胞因子受体相互作用和趋化因子信号通路。最终，我们提出甲磺酸伊马替尼、奥拉替尼、白藜芦醇、索拉非尼和姜黄素可能与Girdin相互作用， potentially contributing to the treatment of liver cancer.