Abstract
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.
Highlights
Worldwide, liver cancer is the fourth most common cause of cancer-related death and ranks sixth in terms of incident cases (Villanueva, 2019)
The Neuroepithelial transforming gene 1 (NET-1) protein functions of Hepatocellular carcinoma (HCC) were investigated in vivo (Wu et al, 2019)
The expression of NET-1 protein in HCC xenograft was merely detected by IHC staining
Summary
Liver cancer is the fourth most common cause of cancer-related death and ranks sixth in terms of incident cases (Villanueva, 2019). Yumita first reported sonodynamic therapy (SDT) (Yumita et al, 1989), which is based on the photodynamic therapy (PDT). This noninvasive treatment technology has already been known as a new anticancer strategy which uses nonthermal ultrasound energy in combination with sonosensitizer agents (Brown et al, 2004; Castano et al, 2004; Rosenthal et al, 2004; McHale et al, 2016). The sonosensitizer agents together with ultrasound irradiation generate reactive oxygen species (ROS) that could induce cancer cell death under aerobic conditions (Yumita et al, 2010; Yumita et al, 2012)
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