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Silencing P2X7 receptor downregulates the expression of TCP-1 involved in lymphoma lymphatic metastasis
Xudong Jiang1, Wenjuan Mao1, Ziyi Yang1
1Department of Clinical Biochemistry, College of Laboratory Diagnostic Medicine, Dalian Medical University, Dalian 116044, China.
Abstract:
P2X7R is an ATP-gated cation channel that participates in cell proliferation and apoptosis. TCP-1 assists with the protein folding. According to our previous research, the P2X7R has a potential role in P388D1 lymphoid neoplasm cells dissemination to peripheral lymph nodes. In order to make a further exploration about the probable mechanism, the lymph nodes which metastasized by P2X7R-silenced P388D1 cells or non-silenced cells were analyzed by 2DE and a MALDI-TOF-based proteomics approach. In the 64 proteins which were differentially expressed between two groups, TCP-1 was found to be significantly decreased in P2X7R shRNA group compared to controls. This correlation was also found in subsequent experiments in vivo and in vitro. The positive correlation between P2X7R and TCP-1 was also proved in both lymphoma and benign lymphadenopathy tissues from patients. It indicates that TCP-1 may be a crucial downstream molecular of P2X7R and plays a novel role in lymphoid neoplasm metastasis.
Insights
The P2X7 receptor (P2X7R) may influence lymphoid neoplasm metastasis. Researchers found that TCP-1 protein levels decrease when P2X7R is silenced, suggesting TCP-1 is a key downstream molecule in this process.
Area of Science:
- Molecular Biology
- Cancer Research
- Proteomics
Background:
- The P2X7 receptor (P2X7R), an ATP-gated cation channel, is involved in cell proliferation and apoptosis.
- Previous research suggests P2X7R plays a role in the dissemination of P388D1 lymphoid neoplasm cells to peripheral lymph nodes.
Purpose of the Study:
- To investigate the underlying mechanism of P2X7R's role in lymphoid neoplasm metastasis.
- To identify downstream molecular targets of P2X7R involved in cancer cell dissemination.
Main Methods:
- Proteomic analysis using 2D electrophoresis (2DE) and MALDI-TOF mass spectrometry.
- Analysis of lymph nodes from mice with P388D1 lymphoid neoplasm cells (P2X7R-silenced vs. non-silenced).
- In vivo and in vitro experiments to validate findings in patient tissues.
Main Results:
- Proteomics identified 64 differentially expressed proteins between P2X7R-silenced and control groups.
- TCP-1 (T-complex polypeptide 1) was significantly decreased in P2X7R-silenced cells.
- A positive correlation between P2X7R and TCP-1 expression was confirmed in mouse models and human lymphoma/lymphadenopathy tissues.
Conclusions:
- TCP-1 is a potential downstream molecular target of P2X7R.
- TCP-1 may play a novel role in the metastasis of lymphoid neoplasms.
- P2X7R-TCP-1 pathway warrants further investigation for therapeutic strategies in lymphoid cancers.
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