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.