{"title":"Knockdown of <i>PAK1IP1</i> can Induce Pyroptosis to Inhibit the Progression of Hepatocellular Carcinoma.","authors":"Xiaoliang Lu, Jie Chen, Zefa Lu, Hong Zang","doi":"10.31083/FBL26654","DOIUrl":null,"url":null,"abstract":"<p><strong>Aim: </strong>To identify potential prognostic biomarkers and uncover new mechanisms underlying hepatocellular carcinoma (HCC).</p><p><strong>Background: </strong>HCC is a prevalent and fatal malignancy originating from hepatic cells, with a consistently rising incidence in recent decades.</p><p><strong>Objective: </strong>To identify potential prognostic biomarkers, specifically focusing on the role of PAK1-interacting protein 1 (PAK1IP1), and to uncover novel mechanistic insights in HCC.</p><p><strong>Methods: </strong>HCC-related datasets (GSE45267 and GSE49515) and data from The Cancer Genome Atlas (TCGA) were retrieved for the analysis of differentially expressed genes (DEGs). The common DEGs were subsequently subjected to weighted gene co-expression network analysis (WGCNA), protein-protein interaction network (PPI), risk model, expression, survival, and prognostic nomogram to determine key genes associated with HCC. Further, the key gene was analyzed using clinical feature analysis, immunoassay, and cell experiments to investigate its exact role in HCC.</p><p><strong>Results: </strong>Based on the above comprehensive analysis, we targeted the key gene <i>PAK1IP1</i> with a good prognostic value in HCC. <i>PAK1IP1</i> showed a remarkably higher increase in tumor samples than in normal samples, which might be related to immune cell infiltration in liver cancer. It was up-regulated in HCC cells, and its knockdown could suppress HCC proliferation and migration. Besides, enzyme-linked immunosorbent assay (ELISA) showed that <i>PAK1IP1</i> could regulate lipopolysaccharide (LPS)-induced pyroptosis of HCC cells. Knocking down <i>PAK1IP1</i> could lead to increased expression of caspase 3 (CASP-3), gasdermin E (GSDME)-N, cleaved caspase-1, and gasdermin-D (GSDMD)-N in HCC cells, inducing pyroptosis, thereby inhibiting the development of HCC.</p><p><strong>Conclusion: </strong>To summarize, <i>PAK1IP1</i> was identified as a promising prognostic biomarker, and the knockdown of <i>PAK1IP1</i> can induce pyroptosis to suppress HCC development, which sheds new light on HCC tumorigenesis.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 4","pages":"26654"},"PeriodicalIF":3.3000,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in bioscience (Landmark edition)","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.31083/FBL26654","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Aim: To identify potential prognostic biomarkers and uncover new mechanisms underlying hepatocellular carcinoma (HCC).
Background: HCC is a prevalent and fatal malignancy originating from hepatic cells, with a consistently rising incidence in recent decades.
Objective: To identify potential prognostic biomarkers, specifically focusing on the role of PAK1-interacting protein 1 (PAK1IP1), and to uncover novel mechanistic insights in HCC.
Methods: HCC-related datasets (GSE45267 and GSE49515) and data from The Cancer Genome Atlas (TCGA) were retrieved for the analysis of differentially expressed genes (DEGs). The common DEGs were subsequently subjected to weighted gene co-expression network analysis (WGCNA), protein-protein interaction network (PPI), risk model, expression, survival, and prognostic nomogram to determine key genes associated with HCC. Further, the key gene was analyzed using clinical feature analysis, immunoassay, and cell experiments to investigate its exact role in HCC.
Results: Based on the above comprehensive analysis, we targeted the key gene PAK1IP1 with a good prognostic value in HCC. PAK1IP1 showed a remarkably higher increase in tumor samples than in normal samples, which might be related to immune cell infiltration in liver cancer. It was up-regulated in HCC cells, and its knockdown could suppress HCC proliferation and migration. Besides, enzyme-linked immunosorbent assay (ELISA) showed that PAK1IP1 could regulate lipopolysaccharide (LPS)-induced pyroptosis of HCC cells. Knocking down PAK1IP1 could lead to increased expression of caspase 3 (CASP-3), gasdermin E (GSDME)-N, cleaved caspase-1, and gasdermin-D (GSDMD)-N in HCC cells, inducing pyroptosis, thereby inhibiting the development of HCC.
Conclusion: To summarize, PAK1IP1 was identified as a promising prognostic biomarker, and the knockdown of PAK1IP1 can induce pyroptosis to suppress HCC development, which sheds new light on HCC tumorigenesis.
目的：鉴定潜在的预后生物标志物，揭示肝细胞癌（HCC）的新机制。背景：HCC是一种起源于肝细胞的常见和致命的恶性肿瘤，近几十年来发病率持续上升。目的：确定潜在的预后生物标志物，特别关注pak1相互作用蛋白1 （PAK1IP1）的作用，并揭示新的机制见解。方法：检索hcc相关数据集（GSE45267和GSE49515）和来自癌症基因组图谱（TCGA）的数据，分析差异表达基因（DEGs）。随后，对常见的deg进行加权基因共表达网络分析（WGCNA）、蛋白-蛋白相互作用网络（PPI）、风险模型、表达、生存和预后图分析，以确定与HCC相关的关键基因。进一步，通过临床特征分析、免疫分析和细胞实验对关键基因进行分析，以探讨其在HCC中的确切作用。结果：在以上综合分析的基础上，我们锁定了在HCC中具有良好预后价值的关键基因PAK1IP1。PAK1IP1在肿瘤样品中的表达明显高于正常样品，这可能与肝癌免疫细胞浸润有关。它在HCC细胞中表达上调，敲低它可以抑制HCC的增殖和迁移。此外，酶联免疫吸附试验（ELISA）显示PAK1IP1可调节脂多糖（LPS）诱导的肝癌细胞焦亡。敲低PAK1IP1可导致HCC细胞中caspase 3 （CASP-3）、gasdermin E (GSDME)-N、cleaved caspase-1、gasdermin- d (GSDMD)-N的表达增加，诱导细胞焦亡，从而抑制HCC的发展。结论：综上所述，PAK1IP1是一种很有前景的预后生物标志物，敲低PAK1IP1可诱导细胞焦亡，从而抑制HCC的发展，为HCC的发生机制研究提供了新的思路。
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
