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SYNJ2BP inhibits tumor growth and metastasis by activating DLL4 pathway in hepatocellular carcinoma
Xiao Liu1, Jiangjiao Zhou1, Ning Zhou2
1Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China.
Background:
Synaptojanin 2 Binding Protein (SYNJ2BP) is essential to cell proliferation. Previous studies show that SYNJ2BP participates in sprouting angiogenesis, which plays an important part in several abnormal conditions including cancer. However, the activity of SYNJ2BP in hepatocellular carcinoma (HCC) has not been elucidated yet.
Methods:
Firstly, real-time PCR and western blotting (WB) were adopted to evaluate SYNJ2BP expressions in HCC tissues and HCC cell lines. Secondly, we did follow-up and prognostic study to explore the association of SYNJ2BP expression and HCC patients prognosis. Thirdly, we induced or silenced SYNJ2BP expression on selected HCC cell lines and explored the function of SYNJ2BP in vitro and in vivo. Lastly, we conducted Cignal Finder Cancer 10-Pathway Reporter Array in combination with loss- and gain-of-function assay to investigate potential mechanisms.
Results:
Through various techniques we found that SYNJ2BP was decreased in HCC tissues and HCC cell lines. The subsequent analysis showed that low expression of SYNJ2BP was associated with tumor size, tumor nodule number, vascular invasion, TNM stage and BCLC stage, and was an independent risk factor for survival of HCC. Later, the in vitro experiments demonstrated that SYNJ2BP inhibited HCC cells invasion, migration and proliferation, also the in vivo testing revealed that SYNJ2BP inhibited tumor growth and metastasis. Finally, we also uncovered that SYNJ2BP inhibited HCC growth and metastasis through activating DLL4-mediated Notch signaling pathway.
Conclusions:
Collectively, our data provide evidence that SYNJ2BP may act as a tumor suppressor during HCC development and could serve as a potential therapeutic target.
Insights
Synaptojanin 2 Binding Protein (SYNJ2BP) acts as a tumor suppressor in hepatocellular carcinoma (HCC). Lower SYNJ2BP levels correlate with poor prognosis, and restoring its expression inhibits HCC growth and metastasis.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Synaptojanin 2 Binding Protein (SYNJ2BP) is crucial for cell proliferation and angiogenesis.
- Its role in hepatocellular carcinoma (HCC) remains largely uncharacterized.
- Angiogenesis is implicated in various cancers, including HCC.
Purpose of the Study:
- To investigate the expression and function of SYNJ2BP in HCC.
- To determine the prognostic significance of SYNJ2BP in HCC patients.
- To elucidate the underlying molecular mechanisms of SYNJ2BP's action in HCC.
Main Methods:
- SYNJ2BP expression was quantified in HCC tissues and cell lines using real-time PCR and Western blotting.
- Prognostic analysis was performed on HCC patient data.
- In vitro and in vivo functional assays were conducted by manipulating SYNJ2BP levels.
- Pathway analysis was employed to identify molecular mechanisms.
Main Results:
- SYNJ2BP expression was significantly decreased in HCC tissues and cell lines.
- Low SYNJ2BP expression correlated with advanced tumor stage, vascular invasion, and poorer patient survival.
- SYNJ2BP suppressed HCC cell invasion, migration, and proliferation in vitro and inhibited tumor growth and metastasis in vivo.
- SYNJ2BP was found to activate the DLL4-mediated Notch signaling pathway.
Conclusions:
- SYNJ2BP functions as a tumor suppressor in HCC development.
- SYNJ2BP may serve as a potential therapeutic target for HCC.
- Restoring SYNJ2BP expression could inhibit HCC progression.
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