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Published on: October 6, 2019
The clinical significance and biological function of interferon regulatory factor 1 in cholangiocarcinoma
Peiqi Wan1, Junhong Zhang2, Qiang Du3
1Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USA; Department of infectious diseases, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, PR China.
Abstract:
Interferon regulatory factor 1 (IRF1) has been suggested to act as a tumor suppressor in human cancers. However, the clinical significance and biological function of IRF1 in cholangiocarcinoma is poorly understood. In our results, IRF1 mRNA and protein expressions were decreased in cholangiocarcinoma tissues and cell lines compared with paired normal hepatic tissues and intrahepatic bile duct epithelial cell line. IRF1 protein low-expression was associated with tumor stage, tumor size, vascular invasion and metastasis and served as a poor independent prognostic parameter in cholangiocarcinoma patients. Up-regulation of IRF1 expression suppressed cholangiocarcinoma cells proliferation, migration and invasion, and blocked cell cycle progression, but has no effect on apoptosis. In conclusion, IRF1 is low-expressed in cholangiocarcinoma tissues and cell lines, and correlated with malignant status and prognosis in cholangiocarcinoma patients. IRF1 served as tumor suppressor in the regulation of cholangiocarcinoma cells proliferation, cell cycle, migration and invasion.
Insights
Interferon regulatory factor 1 (IRF1) is downregulated in cholangiocarcinoma, correlating with poor prognosis. Restoring IRF1 suppresses tumor growth, migration, and invasion, supporting its role as a tumor suppressor.
Area of Science:
- Oncology
- Molecular Biology
- Hepatobiliary Surgery
Background:
- Interferon regulatory factor 1 (IRF1) is implicated as a tumor suppressor in various human cancers.
- The specific role and clinical significance of IRF1 in cholangiocarcinoma remain largely uncharacterized.
Purpose of the Study:
- To investigate the expression levels, clinical significance, and biological functions of IRF1 in cholangiocarcinoma.
Main Methods:
- Quantitative analysis of IRF1 mRNA and protein expression in cholangiocarcinoma tissues and cell lines versus normal controls.
- Correlation analysis between IRF1 expression and clinicopathological parameters.
- Functional assays to assess the impact of IRF1 up-regulation on cholangiocarcinoma cell proliferation, migration, invasion, cell cycle, and apoptosis.
Main Results:
- IRF1 mRNA and protein expression were significantly decreased in cholangiocarcinoma tissues and cell lines.
- Low IRF1 protein expression correlated with advanced tumor stage, larger tumor size, vascular invasion, and metastasis.
- IRF1 served as an independent poor prognostic factor for cholangiocarcinoma patients.
- IRF1 up-regulation inhibited cholangiocarcinoma cell proliferation, migration, and invasion, and induced cell cycle arrest without affecting apoptosis.
Conclusions:
- IRF1 is frequently downregulated in cholangiocarcinoma, associated with aggressive disease and poor outcomes.
- IRF1 functions as a tumor suppressor by inhibiting proliferation, migration, invasion, and cell cycle progression in cholangiocarcinoma.
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