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Analyzing Roles of NUSAP1 From Clinical, Molecular Mechanism and Immune Perspectives in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is one of the most common carcinomas worldwide. Our study aims to analyze how NUSAP1 affects progression of HCC from clinical, molecular mechanism and immune perspectives. Firstly, we downloaded GSE62232, GSE102079, GSE112790, and GSE121248 gene expression profile data...

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Autores principales: Zhu, Wenjie, Xu, Jian, Chen, Zehao, Jiang, Jianxin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8329558/
https://www.ncbi.nlm.nih.gov/pubmed/34354737
http://dx.doi.org/10.3389/fgene.2021.689159
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author Zhu, Wenjie
Xu, Jian
Chen, Zehao
Jiang, Jianxin
author_facet Zhu, Wenjie
Xu, Jian
Chen, Zehao
Jiang, Jianxin
author_sort Zhu, Wenjie
collection PubMed
description Hepatocellular carcinoma (HCC) is one of the most common carcinomas worldwide. Our study aims to analyze how NUSAP1 affects progression of HCC from clinical, molecular mechanism and immune perspectives. Firstly, we downloaded GSE62232, GSE102079, GSE112790, and GSE121248 gene expression profile datasets from GEO database. R studio was used to screen DEGs of each dataset, and 86 overlapping DEGs of the four datasets were screened at last. Then, CytoHubba plug-in in Cytoscape software was used to screen out NUSAP1 from the 86 DEGs. Subsequently, survival analysis, clinical correlation analysis, independent prognostic analysis, and GSEA enrichment analysis of NUSAP1 were analyzed using HCC patients from GSE76427 dataset, ICGC database, and TCGA database. The results revealed that HCC patients with higher expression level of NUSAP1 had a worse prognosis. NUSAP1 was an independent prognostic factor of HCC, and it may promote HCC progress by regulating cell cycle. To further elucidate its underlying molecular mechanism, we used cBioProtal online data analysis tool to screen all co-expression genes of NUSAP1 and used top 300 co-expression genes to accomplish KEGG and GO enrichment analysis; the results confirmed that NUSAP1 accelerated progression of HCC by regulating cell cycle. We continued to draw KEGG pathway map of cell cycle using co-expression genes enriched in cell cycle pathway by KEGG online tool. The map depicted that most of co-expression genes of NUSAP1 were located in S phase and G2/M phase of the cell cycle, and they could regulate the genes in G1 phase. To further understand the mechanism of cell cycle, we also did qRT-PCR, Western blot, and flow cytometry; the results showed that NUSAP1 was closely associated with CDK4, CDK6, and cyclinD1, which could regulate G1 to S phase transition. Besides, we also analyzed correlation between NUSAP1 and immune cells using HCC patients from GSE76427 dataset, ICGC database, and TCGA database. NUSAP1 was associated with some immune cells, and we speculated that NUSAP1 could also promote HCC progression by influencing T cell CD4 memory resting and macrophage M0 through some underlying mechanism.
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spelling pubmed-83295582021-08-04 Analyzing Roles of NUSAP1 From Clinical, Molecular Mechanism and Immune Perspectives in Hepatocellular Carcinoma Zhu, Wenjie Xu, Jian Chen, Zehao Jiang, Jianxin Front Genet Genetics Hepatocellular carcinoma (HCC) is one of the most common carcinomas worldwide. Our study aims to analyze how NUSAP1 affects progression of HCC from clinical, molecular mechanism and immune perspectives. Firstly, we downloaded GSE62232, GSE102079, GSE112790, and GSE121248 gene expression profile datasets from GEO database. R studio was used to screen DEGs of each dataset, and 86 overlapping DEGs of the four datasets were screened at last. Then, CytoHubba plug-in in Cytoscape software was used to screen out NUSAP1 from the 86 DEGs. Subsequently, survival analysis, clinical correlation analysis, independent prognostic analysis, and GSEA enrichment analysis of NUSAP1 were analyzed using HCC patients from GSE76427 dataset, ICGC database, and TCGA database. The results revealed that HCC patients with higher expression level of NUSAP1 had a worse prognosis. NUSAP1 was an independent prognostic factor of HCC, and it may promote HCC progress by regulating cell cycle. To further elucidate its underlying molecular mechanism, we used cBioProtal online data analysis tool to screen all co-expression genes of NUSAP1 and used top 300 co-expression genes to accomplish KEGG and GO enrichment analysis; the results confirmed that NUSAP1 accelerated progression of HCC by regulating cell cycle. We continued to draw KEGG pathway map of cell cycle using co-expression genes enriched in cell cycle pathway by KEGG online tool. The map depicted that most of co-expression genes of NUSAP1 were located in S phase and G2/M phase of the cell cycle, and they could regulate the genes in G1 phase. To further understand the mechanism of cell cycle, we also did qRT-PCR, Western blot, and flow cytometry; the results showed that NUSAP1 was closely associated with CDK4, CDK6, and cyclinD1, which could regulate G1 to S phase transition. Besides, we also analyzed correlation between NUSAP1 and immune cells using HCC patients from GSE76427 dataset, ICGC database, and TCGA database. NUSAP1 was associated with some immune cells, and we speculated that NUSAP1 could also promote HCC progression by influencing T cell CD4 memory resting and macrophage M0 through some underlying mechanism. Frontiers Media S.A. 2021-07-20 /pmc/articles/PMC8329558/ /pubmed/34354737 http://dx.doi.org/10.3389/fgene.2021.689159 Text en Copyright © 2021 Zhu, Xu, Chen and Jiang. https://creativecommons.org/licenses/by/4.0/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) and the copyright owner(s) 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.
spellingShingle Genetics
Zhu, Wenjie
Xu, Jian
Chen, Zehao
Jiang, Jianxin
Analyzing Roles of NUSAP1 From Clinical, Molecular Mechanism and Immune Perspectives in Hepatocellular Carcinoma
title Analyzing Roles of NUSAP1 From Clinical, Molecular Mechanism and Immune Perspectives in Hepatocellular Carcinoma
title_full Analyzing Roles of NUSAP1 From Clinical, Molecular Mechanism and Immune Perspectives in Hepatocellular Carcinoma
title_fullStr Analyzing Roles of NUSAP1 From Clinical, Molecular Mechanism and Immune Perspectives in Hepatocellular Carcinoma
title_full_unstemmed Analyzing Roles of NUSAP1 From Clinical, Molecular Mechanism and Immune Perspectives in Hepatocellular Carcinoma
title_short Analyzing Roles of NUSAP1 From Clinical, Molecular Mechanism and Immune Perspectives in Hepatocellular Carcinoma
title_sort analyzing roles of nusap1 from clinical, molecular mechanism and immune perspectives in hepatocellular carcinoma
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8329558/
https://www.ncbi.nlm.nih.gov/pubmed/34354737
http://dx.doi.org/10.3389/fgene.2021.689159
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