Identification of anoikis-related genes in heart failure: bioinformatics and experimental validation.

IF 2.5 3区生物学

Hereditas Pub Date : 2025-08-16 DOI:10.1186/s41065-025-00532-2

Lina Zhang, Jianjun Gu, Yan Jiang, Juan Xue, Ye Zhu

{"title":"Identification of anoikis-related genes in heart failure: bioinformatics and experimental validation.","authors":"Lina Zhang, Jianjun Gu, Yan Jiang, Juan Xue, Ye Zhu","doi":"10.1186/s41065-025-00532-2","DOIUrl":null,"url":null,"abstract":"Background: Heart failure (HF) is a common clinical syndrome caused by ventricular dysfunction and one of the leading causes of mortality worldwide. Previous studies have suggested that anoikis is relevant to HF. This study aimed to identify hub genes associated with anoikis that may offer therapeutic targets for HF.Materials and methods: Gene expression data for GSE36074 were obtained from the Gene Expression Omnibus (GEO) and anoikis-related genes (ARGs) were extracted from GeneCards. GEO2R was used to screen for differentially expressed genes (DEGs), then by overlapping DEGs with ARGs, differentially expressed ARGs (DEARGs) were screened. The biological functions of the DEARGs were determined using DAVID. Subsequently, two machine learning (ML) algorithms were employed to identify hub DEARGs: least absolute shrinkage and selection operator (LASSO) and random forest (RF). In addition, miRNA-hub DEARGs and drug-hub DEARGs networks were constructed. Lastly, the hub DEARGs were validated by quantitative reverse transcription PCR (RT-qPCR) and Immunofluorescence (IF).Results: A total of 138 DEARGs were identified in GSE36074. Functional analysis of DEARGs revealed that they were primarily enriched in the positive regulation of the apoptotic process, PI3K-Akt, and FoxO signaling pathways. Subsequently, two hub DEARGs (Tln1 and TGFβ2) were screened using LASSO and RF algorithms. According to the miRNA-hub DEARGs networks, Tln1 and TGFβ2 were regulated by 34 and 68 miRNAs, respectively. Moreover, drug-hub DEARGs networks showed that Gemogenovatucel-t, Lerdelimumab, Belagenpumatucel-l, Fresolimumab, Bintrafusp alfa, Trabedersen and Luspatercept-aamt are potential drugs that could target TGFβ2. Finally, RT-qPCR and IF validation of two key DEARGs (Tln1 and TGFβ2) supported our bioinformatics analysis.Conclusions: These findings suggest that Tln1 and TGFβ2 may play important roles in HF development through the regulation of anoikis and may serve as therapeutic targets for HF.Clinical trial number: Not applicable.","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":"162 1","pages":"163"},"PeriodicalIF":2.5000,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12357471/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Hereditas","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1186/s41065-025-00532-2","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}

引用次数: 0

Abstract

Background: Heart failure (HF) is a common clinical syndrome caused by ventricular dysfunction and one of the leading causes of mortality worldwide. Previous studies have suggested that anoikis is relevant to HF. This study aimed to identify hub genes associated with anoikis that may offer therapeutic targets for HF.

Materials and methods: Gene expression data for GSE36074 were obtained from the Gene Expression Omnibus (GEO) and anoikis-related genes (ARGs) were extracted from GeneCards. GEO2R was used to screen for differentially expressed genes (DEGs), then by overlapping DEGs with ARGs, differentially expressed ARGs (DEARGs) were screened. The biological functions of the DEARGs were determined using DAVID. Subsequently, two machine learning (ML) algorithms were employed to identify hub DEARGs: least absolute shrinkage and selection operator (LASSO) and random forest (RF). In addition, miRNA-hub DEARGs and drug-hub DEARGs networks were constructed. Lastly, the hub DEARGs were validated by quantitative reverse transcription PCR (RT-qPCR) and Immunofluorescence (IF).

Results: A total of 138 DEARGs were identified in GSE36074. Functional analysis of DEARGs revealed that they were primarily enriched in the positive regulation of the apoptotic process, PI3K-Akt, and FoxO signaling pathways. Subsequently, two hub DEARGs (Tln1 and TGFβ2) were screened using LASSO and RF algorithms. According to the miRNA-hub DEARGs networks, Tln1 and TGFβ2 were regulated by 34 and 68 miRNAs, respectively. Moreover, drug-hub DEARGs networks showed that Gemogenovatucel-t, Lerdelimumab, Belagenpumatucel-l, Fresolimumab, Bintrafusp alfa, Trabedersen and Luspatercept-aamt are potential drugs that could target TGFβ2. Finally, RT-qPCR and IF validation of two key DEARGs (Tln1 and TGFβ2) supported our bioinformatics analysis.

Conclusions: These findings suggest that Tln1 and TGFβ2 may play important roles in HF development through the regulation of anoikis and may serve as therapeutic targets for HF.

Clinical trial number: Not applicable.

查看原文本刊更多论文

心衰中嗜酒相关基因的鉴定：生物信息学和实验验证。

背景：心力衰竭（HF）是由心室功能障碍引起的常见临床综合征，也是世界范围内死亡的主要原因之一。先前的研究表明，anoikis与HF有关。本研究旨在鉴定与心衰相关的中枢基因，这些基因可能为心衰提供治疗靶点。材料和方法：GSE36074基因表达数据来源于Gene expression Omnibus (GEO)， anoiki相关基因（ARGs）来源于GeneCards。采用GEO2R筛选差异表达基因（differential expression genes, deg），再通过deg与ARGs重叠，筛选差异表达基因（differential expression ARGs, DEARGs）。采用DAVID法测定了DEARGs的生物学功能。随后，采用两种机器学习（ML）算法来识别轮毂dearg：最小绝对收缩和选择算子（LASSO）和随机森林（RF）。此外，还构建了miRNA-hub DEARGs和drug-hub DEARGs网络。最后，通过定量反转录PCR （RT-qPCR）和免疫荧光（IF）验证枢纽DEARGs。结果：GSE36074共鉴定出138个DEARGs。对DEARGs的功能分析显示，它们主要富集于细胞凋亡过程、PI3K-Akt和FoxO信号通路的正调控。随后，使用LASSO和RF算法筛选两个枢纽DEARGs （Tln1和TGFβ2）。根据miRNA-hub DEARGs网络，Tln1和tgf - β2分别受34和68个mirna调控。此外，药物中心DEARGs网络显示，Gemogenovatucel-t、Lerdelimumab、belagenpumatucel - 1、Fresolimumab、Bintrafusp alfa、Trabedersen和luspaterept -aamt是可能靶向tgf - β2的潜在药物。最后，两个关键DEARGs （Tln1和TGFβ2）的RT-qPCR和IF验证支持了我们的生物信息学分析。结论：这些发现提示Tln1和TGFβ2可能通过调节anoikis在HF的发展中发挥重要作用，并可能作为HF的治疗靶点。临床试验号：不适用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Hereditas Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

3.80

自引率

3.70%

发文量

期刊介绍： For almost a century, Hereditas has published original cutting-edge research and reviews. As the Official journal of the Mendelian Society of Lund, the journal welcomes research from across all areas of genetics and genomics. Topics of interest include human and medical genetics, animal and plant genetics, microbial genetics, agriculture and bioinformatics.