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Quantitative Proteomics Analysis of FFPE Tumor Samples Reveals the Influences of NET-1 siRNA Nanoparticles and Sonodynamic Therapy on Tetraspanin Protein Involved in HCC

Hepatocellular carcinoma (HCC) poses a severe threat to human health. The NET-1 protein has been proved to be strongly associated with HCC proliferation and metastasis in our previous study. Here, we established and validated the NET-1 siRNA nanoparticles system to conduct targeted gene therapy of H...

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Autores principales: Wu, Bolin, Shang, Haitao, Liu, Jiayin, Liang, Xitian, Yuan, Yanchi, Chen, Yichi, Wang, Chunyue, Jing, Hui, Cheng, Wen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141748/
https://www.ncbi.nlm.nih.gov/pubmed/34041269
http://dx.doi.org/10.3389/fmolb.2021.678444
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author Wu, Bolin
Shang, Haitao
Liu, Jiayin
Liang, Xitian
Yuan, Yanchi
Chen, Yichi
Wang, Chunyue
Jing, Hui
Cheng, Wen
author_facet Wu, Bolin
Shang, Haitao
Liu, Jiayin
Liang, Xitian
Yuan, Yanchi
Chen, Yichi
Wang, Chunyue
Jing, Hui
Cheng, Wen
author_sort Wu, Bolin
collection PubMed
description Hepatocellular carcinoma (HCC) poses a severe threat to human health. The NET-1 protein has been proved to be strongly associated with HCC proliferation and metastasis in our previous study. Here, we established and validated the NET-1 siRNA nanoparticles system to conduct targeted gene therapy of HCC xenograft in vivo with the aid of sonodynamic therapy. Then, we conducted a label-free proteome mass spectrometry workflow to analyze formalin-fixed and paraffin-embedded HCC xenograft samples collected in this study. The result showed that 78 proteins were differentially expressed after NET-1 protein inhibited. Among them, the expression of 17 proteins upregulated and the expression of 61 proteins were significantly downregulated. Of the protein abundance, the vast majority of Gene Ontology enrichment terms belong to the biological process. The KEGG pathway enrichment analysis showed that the 78 differentially expressed proteins significantly enriched in 45 pathways. We concluded that the function of the NET-1 gene is not only to regulate HCC but also to participate in a variety of biochemical metabolic pathways in the human body. Furthermore, the protein–protein interaction analysis indicated that the interactions of differentially expressed proteins are incredibly sophisticated. All the protein–protein interactions happened after the NET-1 gene has been silenced. Finally, our study also provides a useful proposal for targeted therapy based on tetraspanin proteins to treat HCC, and further mechanism investigations are needed to reveal a more detailed mechanism of action for NET-1 protein regulation of HCC.
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spelling pubmed-81417482021-05-25 Quantitative Proteomics Analysis of FFPE Tumor Samples Reveals the Influences of NET-1 siRNA Nanoparticles and Sonodynamic Therapy on Tetraspanin Protein Involved in HCC Wu, Bolin Shang, Haitao Liu, Jiayin Liang, Xitian Yuan, Yanchi Chen, Yichi Wang, Chunyue Jing, Hui Cheng, Wen Front Mol Biosci Molecular Biosciences Hepatocellular carcinoma (HCC) poses a severe threat to human health. The NET-1 protein has been proved to be strongly associated with HCC proliferation and metastasis in our previous study. Here, we established and validated the NET-1 siRNA nanoparticles system to conduct targeted gene therapy of HCC xenograft in vivo with the aid of sonodynamic therapy. Then, we conducted a label-free proteome mass spectrometry workflow to analyze formalin-fixed and paraffin-embedded HCC xenograft samples collected in this study. The result showed that 78 proteins were differentially expressed after NET-1 protein inhibited. Among them, the expression of 17 proteins upregulated and the expression of 61 proteins were significantly downregulated. Of the protein abundance, the vast majority of Gene Ontology enrichment terms belong to the biological process. The KEGG pathway enrichment analysis showed that the 78 differentially expressed proteins significantly enriched in 45 pathways. We concluded that the function of the NET-1 gene is not only to regulate HCC but also to participate in a variety of biochemical metabolic pathways in the human body. Furthermore, the protein–protein interaction analysis indicated that the interactions of differentially expressed proteins are incredibly sophisticated. All the protein–protein interactions happened after the NET-1 gene has been silenced. Finally, our study also provides a useful proposal for targeted therapy based on tetraspanin proteins to treat HCC, and further mechanism investigations are needed to reveal a more detailed mechanism of action for NET-1 protein regulation of HCC. Frontiers Media S.A. 2021-05-10 /pmc/articles/PMC8141748/ /pubmed/34041269 http://dx.doi.org/10.3389/fmolb.2021.678444 Text en Copyright © 2021 Wu, Shang, Liu, Liang, Yuan, Chen, Wang, Jing and Cheng. 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 Molecular Biosciences
Wu, Bolin
Shang, Haitao
Liu, Jiayin
Liang, Xitian
Yuan, Yanchi
Chen, Yichi
Wang, Chunyue
Jing, Hui
Cheng, Wen
Quantitative Proteomics Analysis of FFPE Tumor Samples Reveals the Influences of NET-1 siRNA Nanoparticles and Sonodynamic Therapy on Tetraspanin Protein Involved in HCC
title Quantitative Proteomics Analysis of FFPE Tumor Samples Reveals the Influences of NET-1 siRNA Nanoparticles and Sonodynamic Therapy on Tetraspanin Protein Involved in HCC
title_full Quantitative Proteomics Analysis of FFPE Tumor Samples Reveals the Influences of NET-1 siRNA Nanoparticles and Sonodynamic Therapy on Tetraspanin Protein Involved in HCC
title_fullStr Quantitative Proteomics Analysis of FFPE Tumor Samples Reveals the Influences of NET-1 siRNA Nanoparticles and Sonodynamic Therapy on Tetraspanin Protein Involved in HCC
title_full_unstemmed Quantitative Proteomics Analysis of FFPE Tumor Samples Reveals the Influences of NET-1 siRNA Nanoparticles and Sonodynamic Therapy on Tetraspanin Protein Involved in HCC
title_short Quantitative Proteomics Analysis of FFPE Tumor Samples Reveals the Influences of NET-1 siRNA Nanoparticles and Sonodynamic Therapy on Tetraspanin Protein Involved in HCC
title_sort quantitative proteomics analysis of ffpe tumor samples reveals the influences of net-1 sirna nanoparticles and sonodynamic therapy on tetraspanin protein involved in hcc
topic Molecular Biosciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141748/
https://www.ncbi.nlm.nih.gov/pubmed/34041269
http://dx.doi.org/10.3389/fmolb.2021.678444
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