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ORIGINAL RESEARCH article
Front. Oncol.
Sec. Molecular and Cellular Oncology
Volume 14 - 2024 |
doi: 10.3389/fonc.2024.1446324
This article is part of the Research Topic Signaling Transduction of Innate Immunity and Regulation Mechanisms in the Tumor Immune Microenvironment View all articles
Identify BCAT1 plays an oncogenic role and promotes EMT in KIRC via single cell RNA-seq and experiment
Provisionally accepted- The First Affiliated Hospital of Soochow University, Suzhou, China
Background: Kidney renal clear cell carcinoma (KIRC) is a major subtype of renal cell carcinoma with poor prognosis due to its invasive and metastatic nature. Despite advances in understanding the molecular underpinnings of various cancers, the role of branched-chain amino acid transferase 1 (BCAT1) in KIRC remains underexplored. This study aims to fill this gap by investigating the oncogenic role of BCAT1 in KIRC using single-cell RNA-seq data and experimental validation.Methods: Single-cell transcriptomic data GSE159115 was utilized to investigate potential biomarkers in KIRC. After screening, we used BCAT1 as a target gene and investigated its function and mechanism in KIRC through databases such as TCGA-GTEx, using genome enrichment analysis (GSEA), genome variation analysis (GSVA), gene ontology (GO) and Kyoto Encyclopedia of the Genome (KEGG).BCAT1 expression was detected in clinical tissue samples using Western Blotting (WB) and immunohistochemical (IHC) staining techniques. We established cell lines stably overexpressing and knocking down BCAT1 and performed WB, qRT-PCR, cell scratch assay and transwell assay.Results: BCAT1 was highly expressed in KIRC and was associated with disease prognosis and TME.Patients with mutations in the BCAT1 gene had shorter overall survival (OS) and disease-free survival (DFS). patients with high BCAT1 expression had shorter OS, progression-free interval (PFI), and disease-specific survival (DSS). GSEA showed that BCAT1 was significantly enriched in epithelial mesenchymal transition (EMT). Bioinformatics analysis and WB and IHC staining showed that BCAT1 expression was higher in KIRC than in paracancerous tissues. In vitro experiments confirmed that BCAT1 in KIRC cells may promote EMT affecting its invasion, migration. We constructed a protein interaction network (PPI) to hypothesize proteins that may interact with BCAT1. Single-sample gene set enrichment analysis (ssGSEA) revealed the immune infiltration environment of BCAT1.Furthermore, hypomethylation of the BCAT1 promoter region in KIRC may contribute to disease progression by promoting BCAT1 expression.BCAT1 promotes KIRC invasion and metastasis through EMT and has prognostic predictive value and potential as a biomarker. It may become a novel biomarker.
Keywords: BCAT1, Renal cell carcinoma, EMT, biomarker, Tumor immune microenvironment
Received: 09 Jun 2024; Accepted: 26 Aug 2024.
Copyright: © 2024 Li, Guo, Zhu, Sun and Zhou. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Yinsheng Guo, The First Affiliated Hospital of Soochow University, Suzhou, China
Guanhua Zhu, The First Affiliated Hospital of Soochow University, Suzhou, China
Lu Sun, The First Affiliated Hospital of Soochow University, Suzhou, China
Feng Zhou, The First Affiliated Hospital of Soochow University, Suzhou, China
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