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TPX2 level correlates with cholangiocarcinoma cell proliferation, apoptosis, and EMT
Zhenhong Zou1, Bingbing Zheng1, Jiaxi Li1
1Department of General Surgery, the Second Affiliated Hospital of Nanchang University, Nanchang, China.
Purpose:
The molecular signatures of cholangiocarcinoma are not well characterized. Targeting protein for Xenopus kinesin-like protein 2 (TPX2) has been shown to promote oncogenesis in the context of several cancers; however, its' role in cholangiocarcinoma has not been studied. We evaluated the role of TPX2 in cholangiocarcinoma.
Methods:
Expression levels of TPX2 in cholangiocarcinoma were assessed by immunohistochemistry. Potential correlations were assessed by Chi-squared test. Impact of TPX2 expression on cell proliferation, cell cycle, apoptosis, cell invasion and migration was investigated by CCK-8, flow cytometric analysis, and transwell assay, respectively. The expressions of cell-cycle, cell-apoptosis and EMT related target proteins were detected by immunoblotting.
Results:
TPX2 expression in cholangiocarcinoma tissues was significantly higher than that paracancerous tissue (44.3% vs. 5.7%; P<0.01). Overexpression of TPX2 showed a positive correlation with TNM stage, lymph node metastasis, and prognosis of patients. Knockdown of TPX2 expression induced G2-M arrest, apoptosis and inhibited invasion and migration of cholangiocarcinoma cells. Treatment of cholangiocarcinoma cells with TPX2 siRNA resulted in upregulation of cyclin A1, cyclin B1, p53, Bax, and E-cadherin; while downregulation of cyclin D1, CDK2, Bcl-2, N-cadherin, β-cadherin MMP-2, MMP-9, Slug, and Twist1.
Conclusions:
Collectively, these results indicate that TPX2 may serve as a potential biomarker of prognostic relevance and a potential therapeutic target for cholangiocarcinoma.
Insights
Targeting protein for Xenopus kinesin-like protein 2 (TPX2) is elevated in cholangiocarcinoma, correlating with poor prognosis. Inhibiting TPX2 suppresses cancer cell growth, suggesting it as a therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Cholangiocarcinoma (CCA) molecular signatures remain poorly understood.
- Targeting protein for Xenopus kinesin-like protein 2 (TPX2) is implicated in oncogenesis across various cancers.
- The specific role of TPX2 in CCA pathogenesis has not been previously investigated.
Purpose of the Study:
- To investigate the role and clinical significance of TPX2 in cholangiocarcinoma.
- To determine if TPX2 expression correlates with clinicopathological features and patient prognosis in CCA.
- To explore the functional impact of TPX2 on CCA cell behavior.
Main Methods:
- TPX2 expression in CCA tissues was quantified using immunohistochemistry.
- Correlations between TPX2 levels and clinicopathological parameters were analyzed via Chi-squared tests.
- Functional assays including CCK-8, flow cytometry, and transwell assays assessed TPX2's impact on proliferation, cell cycle, apoptosis, invasion, and migration. Protein expression was analyzed by immunoblotting.
Main Results:
- TPX2 expression was significantly higher in CCA tissues compared to adjacent normal tissues (44.3% vs. 5.7%, P<0.01).
- TPX2 overexpression positively correlated with advanced TNM stage, lymph node metastasis, and poorer patient prognosis.
- TPX2 knockdown induced G2-M cell cycle arrest, promoted apoptosis, and inhibited invasion and migration, altering key cell cycle and EMT-related protein expressions.
Conclusions:
- TPX2 is significantly overexpressed in cholangiocarcinoma and is associated with adverse prognostic factors.
- TPX2 plays a crucial role in promoting CCA cell proliferation, cell cycle progression, and metastasis.
- TPX2 represents a potential prognostic biomarker and a promising therapeutic target for cholangiocarcinoma.
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