EIF4A3 serves as a prognostic and immunosuppressive microenvironment factor and inhibits cell apoptosis in bladder cancer

EIF4A3 (Eukaryotic translation initiation factor 4A3 (EIF4A3) was recently recognized as an oncogene; however, its role in BLCA (bladder cancer) remains unclear. We explored EIF4A3 expression and its prognostic value in BLCA in public datasets, including the TCGA (The Cancer Genome Atlas) and GEO (G...

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Main Authors: Bing Hu, Ru Chen, Ming Jiang, Situ Xiong, Xiaoqiang Liu, Bin Fu
Format: Article
Language:English
Published: PeerJ Inc. 2023-05-01
Series:PeerJ
Subjects:
Online Access:https://peerj.com/articles/15309.pdf
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author Bing Hu
Ru Chen
Ming Jiang
Situ Xiong
Xiaoqiang Liu
Bin Fu
author_facet Bing Hu
Ru Chen
Ming Jiang
Situ Xiong
Xiaoqiang Liu
Bin Fu
author_sort Bing Hu
collection DOAJ
description EIF4A3 (Eukaryotic translation initiation factor 4A3 (EIF4A3) was recently recognized as an oncogene; however, its role in BLCA (bladder cancer) remains unclear. We explored EIF4A3 expression and its prognostic value in BLCA in public datasets, including the TCGA (The Cancer Genome Atlas) and GEO (Gene Expression Omnibus). Thereafter, the association between EIF4A3 expression and the infiltration of immune cells and immune-checkpoint expression was determined using TIMER2 (Tumor Immune Estimation Resource 2) tool. Additionally, the impact of EIF4A3 on cellular proliferation and apoptosis events in BLCA cell lines was determined by siRNA technology. In this study, EIF4A3 was found to be significantly upregulated in BLCA, upregulated expression of EIF4A3 was related to poor prognosis, advanced histologic grade, subtype, pathological stage, white race, and poor primary therapy outcome. The immune infiltration analysis revealed that EIF4A3 expression was negatively associated with CD8+ and CD4+ T cells and positively with myeloid-derived suppressor cells, macrophage M2, cancer-associated fibroblasts, and Treg cells. Moreover, EIF4A3 was coexpressed with PD-L1 (programmed cell death 1-ligand 1) and its expression was higher in patients responding to anti-PD-L1 therapy. EIF4A3 knockdown significantly inhibited proliferation and promoted apoptosis in 5,637 and T24 cells. In summary, BLCA patients with elevated EIF4A3 expression had an unfavorable prognosis and immunosuppressive microenvironment, and EIF4A3 may facilitate BLCA progression by promoting cell proliferation and inhibiting apoptosis. Furthermore, our study suggests that EIF4A3 is a potential biomarker and therapeutic target for BLCA.
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spelling doaj.art-b2d0dc892f5c4cedb63f0822643b832b2023-12-03T10:30:09ZengPeerJ Inc.PeerJ2167-83592023-05-0111e1530910.7717/peerj.15309EIF4A3 serves as a prognostic and immunosuppressive microenvironment factor and inhibits cell apoptosis in bladder cancerBing Hu0Ru Chen1Ming Jiang2Situ Xiong3Xiaoqiang Liu4Bin Fu5Department of Urology, The First Affiliated Hospital of Nanchang University, Nanchang, ChinaDepartment of Urology, The First Affiliated Hospital of Nanchang University, Nanchang, ChinaDepartment of Urology, The First Affiliated Hospital of Nanchang University, Nanchang, ChinaDepartment of Urology, The First Affiliated Hospital of Nanchang University, Nanchang, ChinaDepartment of Urology, The First Affiliated Hospital of Nanchang University, Nanchang, ChinaDepartment of Urology, The First Affiliated Hospital of Nanchang University, Nanchang, ChinaEIF4A3 (Eukaryotic translation initiation factor 4A3 (EIF4A3) was recently recognized as an oncogene; however, its role in BLCA (bladder cancer) remains unclear. We explored EIF4A3 expression and its prognostic value in BLCA in public datasets, including the TCGA (The Cancer Genome Atlas) and GEO (Gene Expression Omnibus). Thereafter, the association between EIF4A3 expression and the infiltration of immune cells and immune-checkpoint expression was determined using TIMER2 (Tumor Immune Estimation Resource 2) tool. Additionally, the impact of EIF4A3 on cellular proliferation and apoptosis events in BLCA cell lines was determined by siRNA technology. In this study, EIF4A3 was found to be significantly upregulated in BLCA, upregulated expression of EIF4A3 was related to poor prognosis, advanced histologic grade, subtype, pathological stage, white race, and poor primary therapy outcome. The immune infiltration analysis revealed that EIF4A3 expression was negatively associated with CD8+ and CD4+ T cells and positively with myeloid-derived suppressor cells, macrophage M2, cancer-associated fibroblasts, and Treg cells. Moreover, EIF4A3 was coexpressed with PD-L1 (programmed cell death 1-ligand 1) and its expression was higher in patients responding to anti-PD-L1 therapy. EIF4A3 knockdown significantly inhibited proliferation and promoted apoptosis in 5,637 and T24 cells. In summary, BLCA patients with elevated EIF4A3 expression had an unfavorable prognosis and immunosuppressive microenvironment, and EIF4A3 may facilitate BLCA progression by promoting cell proliferation and inhibiting apoptosis. Furthermore, our study suggests that EIF4A3 is a potential biomarker and therapeutic target for BLCA.https://peerj.com/articles/15309.pdfEIF4A3PrognosisImmune infiltrationApoptosisBladder cancer
spellingShingle Bing Hu
Ru Chen
Ming Jiang
Situ Xiong
Xiaoqiang Liu
Bin Fu
EIF4A3 serves as a prognostic and immunosuppressive microenvironment factor and inhibits cell apoptosis in bladder cancer
PeerJ
EIF4A3
Prognosis
Immune infiltration
Apoptosis
Bladder cancer
title EIF4A3 serves as a prognostic and immunosuppressive microenvironment factor and inhibits cell apoptosis in bladder cancer
title_full EIF4A3 serves as a prognostic and immunosuppressive microenvironment factor and inhibits cell apoptosis in bladder cancer
title_fullStr EIF4A3 serves as a prognostic and immunosuppressive microenvironment factor and inhibits cell apoptosis in bladder cancer
title_full_unstemmed EIF4A3 serves as a prognostic and immunosuppressive microenvironment factor and inhibits cell apoptosis in bladder cancer
title_short EIF4A3 serves as a prognostic and immunosuppressive microenvironment factor and inhibits cell apoptosis in bladder cancer
title_sort eif4a3 serves as a prognostic and immunosuppressive microenvironment factor and inhibits cell apoptosis in bladder cancer
topic EIF4A3
Prognosis
Immune infiltration
Apoptosis
Bladder cancer
url https://peerj.com/articles/15309.pdf
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