Yang Haishen, Feiyu Jiang, Xinxin Si, Dan Sun, Haoran Fei, Dali Wang, Kai Li, Shengwang Du, Wei Hu, Zhong Wang
{"title":"Expression of ALG8 in hepatocellular carcinoma and its diagnostic and prognostic significance.","authors":"Yang Haishen, Feiyu Jiang, Xinxin Si, Dan Sun, Haoran Fei, Dali Wang, Kai Li, Shengwang Du, Wei Hu, Zhong Wang","doi":"10.1080/00365521.2024.2433562","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Alpha-1,3-glucosyltransferase (ALG8), a key enzyme in protein glycosylation, is implicated in the oncogenesis and progression of several human malignancies. This study aimed to define the role of ALG8 in hepatocellular carcinoma (HCC) and uncover its mechanisms of action.</p><p><strong>Methods: </strong>ALG8 expression in HCC and normal tissues was analyzed using the TCGA and GEO databases, validated by RT-qPCR and western blot. Survival outcomes were evaluated <i>via</i> Cox analyses, and ALG8's impact on HCC behavior was examined through functional assays. GO, KEGG, and GSEA identified ALG8-related pathways, validated by biochemical assays.</p><p><strong>Results: </strong>In bioinformatics analyses, ALG8 was overexpressed in HCC tissues (<i>p</i> < 0.05 for all comparisons) and correlated with poorer survival (<i>p</i> = 0.006 and <i>p</i> = 0.025, respectively), establishing its role as an independent prognostic factor. <i>In vitro</i> experiments showed that knockdown of ALG8 reduced HCC cell proliferation, migration, and invasion. Using the STRING platform and TCGA-LIHC dataset, we identified ALG8-interacting genes and their associated differentially expressed genes (DEGs). GO and KEGG analyses further linked ALG8 to genes involved in glycosylation, signal release, and other processes, as well as pathways including neuroactive ligand-receptor interaction and N-Glycan biosynthesis. GSEA, corroborated by western blot and immunofluorescence, points to the Wnt/β-catenin signaling cascade as a probable mechanistic pathway through which ALG8 may modulate HCC progression.</p><p><strong>Conclusion: </strong>Elevated ALG8 expression in HCC is linked to worse outcomes and increased tumor aggressiveness, with silencing ALG8 reducing Wnt/β-catenin signaling, highlighting ALG8 as a potential therapeutic target.</p>","PeriodicalId":21461,"journal":{"name":"Scandinavian Journal of Gastroenterology","volume":" ","pages":"1-11"},"PeriodicalIF":1.6000,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Scandinavian Journal of Gastroenterology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/00365521.2024.2433562","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Alpha-1,3-glucosyltransferase (ALG8), a key enzyme in protein glycosylation, is implicated in the oncogenesis and progression of several human malignancies. This study aimed to define the role of ALG8 in hepatocellular carcinoma (HCC) and uncover its mechanisms of action.
Methods: ALG8 expression in HCC and normal tissues was analyzed using the TCGA and GEO databases, validated by RT-qPCR and western blot. Survival outcomes were evaluated via Cox analyses, and ALG8's impact on HCC behavior was examined through functional assays. GO, KEGG, and GSEA identified ALG8-related pathways, validated by biochemical assays.
Results: In bioinformatics analyses, ALG8 was overexpressed in HCC tissues (p < 0.05 for all comparisons) and correlated with poorer survival (p = 0.006 and p = 0.025, respectively), establishing its role as an independent prognostic factor. In vitro experiments showed that knockdown of ALG8 reduced HCC cell proliferation, migration, and invasion. Using the STRING platform and TCGA-LIHC dataset, we identified ALG8-interacting genes and their associated differentially expressed genes (DEGs). GO and KEGG analyses further linked ALG8 to genes involved in glycosylation, signal release, and other processes, as well as pathways including neuroactive ligand-receptor interaction and N-Glycan biosynthesis. GSEA, corroborated by western blot and immunofluorescence, points to the Wnt/β-catenin signaling cascade as a probable mechanistic pathway through which ALG8 may modulate HCC progression.
Conclusion: Elevated ALG8 expression in HCC is linked to worse outcomes and increased tumor aggressiveness, with silencing ALG8 reducing Wnt/β-catenin signaling, highlighting ALG8 as a potential therapeutic target.
期刊介绍:
The Scandinavian Journal of Gastroenterology is one of the most important journals for international medical research in gastroenterology and hepatology with international contributors, Editorial Board, and distribution