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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doaj-68578b52a27f4776ad5b5b55493c86e72021-05-10T06:41:09ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2021-05-01810.3389/fmolb.2021.678444678444Quantitative Proteomics Analysis of FFPE Tumor Samples Reveals the Influences of NET-1 siRNA Nanoparticles and Sonodynamic Therapy on Tetraspanin Protein Involved in HCCBolin Wu0Bolin Wu1Bolin Wu2Haitao Shang3Jiayin Liu4Jiayin Liu5Xitian Liang6Yanchi Yuan7Yanchi Yuan8Yichi Chen9Yichi Chen10Chunyue Wang11Chunyue Wang12Hui Jing13Wen Cheng14Wen Cheng15Department of Ultrasound, Harbin Medical University Cancer Hospital, Harbin, ChinaDepartment of Interventional Ultrasound, Harbin Medical University Cancer Hospital, Harbin, ChinaInstitute of Cancer Prevention and Treatment, Heilongjiang Academy of Medical Science, Harbin Medical University, Harbin, ChinaDepartment of Ultrasound, Harbin Medical University Cancer Hospital, Harbin, ChinaInstitute of Cancer Prevention and Treatment, Heilongjiang Academy of Medical Science, Harbin Medical University, Harbin, ChinaDepartment of Radiation Oncology, Harbin Medical University Cancer Hospital, Harbin, ChinaDepartment of Ultrasound, Harbin Medical University Cancer Hospital, Harbin, ChinaDepartment of Ultrasound, Harbin Medical University Cancer Hospital, Harbin, ChinaInstitute of Cancer Prevention and Treatment, Heilongjiang Academy of Medical Science, Harbin Medical University, Harbin, ChinaDepartment of Ultrasound, Harbin Medical University Cancer Hospital, Harbin, ChinaInstitute of Cancer Prevention and Treatment, Heilongjiang Academy of Medical Science, Harbin Medical University, Harbin, ChinaDepartment of Ultrasound, Harbin Medical University Cancer Hospital, Harbin, ChinaInstitute of Cancer Prevention and Treatment, Heilongjiang Academy of Medical Science, Harbin Medical University, Harbin, ChinaDepartment of Ultrasound, Harbin Medical University Cancer Hospital, Harbin, ChinaDepartment of Ultrasound, Harbin Medical University Cancer Hospital, Harbin, ChinaDepartment of Interventional Ultrasound, Harbin Medical University Cancer Hospital, Harbin, ChinaHepatocellular 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.https://www.frontiersin.org/articles/10.3389/fmolb.2021.678444/fullhepatocellular carcinomasonodynamic therapytetraspanin proteinmass spectrometryproteomicsultrasound |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Bolin Wu Bolin Wu Bolin Wu Haitao Shang Jiayin Liu Jiayin Liu Xitian Liang Yanchi Yuan Yanchi Yuan Yichi Chen Yichi Chen Chunyue Wang Chunyue Wang Hui Jing Wen Cheng Wen Cheng |
spellingShingle |
Bolin Wu Bolin Wu Bolin Wu Haitao Shang Jiayin Liu Jiayin Liu Xitian Liang Yanchi Yuan Yanchi Yuan Yichi Chen Yichi Chen Chunyue Wang Chunyue Wang Hui Jing Wen Cheng Wen Cheng Quantitative Proteomics Analysis of FFPE Tumor Samples Reveals the Influences of NET-1 siRNA Nanoparticles and Sonodynamic Therapy on Tetraspanin Protein Involved in HCC Frontiers in Molecular Biosciences hepatocellular carcinoma sonodynamic therapy tetraspanin protein mass spectrometry proteomics ultrasound |
author_facet |
Bolin Wu Bolin Wu Bolin Wu Haitao Shang Jiayin Liu Jiayin Liu Xitian Liang Yanchi Yuan Yanchi Yuan Yichi Chen Yichi Chen Chunyue Wang Chunyue Wang Hui Jing Wen Cheng Wen Cheng |
author_sort |
Bolin Wu |
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_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_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_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 |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Molecular Biosciences |
issn |
2296-889X |
publishDate |
2021-05-01 |
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. |
topic |
hepatocellular carcinoma sonodynamic therapy tetraspanin protein mass spectrometry proteomics ultrasound |
url |
https://www.frontiersin.org/articles/10.3389/fmolb.2021.678444/full |
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