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Tumor-suppressive function of UNC5D in papillary thyroid cancer
Man-Man Zhang1, Feng Sun1, Bing Cui2
1The Core Laboratory in Medicine Center of Clinical Research, Department of Endocrinology, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200011, China.
Background:
Studies have shown an association of the UNC5D gene with kidney and bladder cancer and neuroblastoma. We investigated whether UNC5D acts as a tumor suppressor in papillary thyroid carcinoma (PTC).
Methods:
Primary PTC tumors and matched normal thyroid tissues were obtained from 112 patients to detect UNC5D mRNA by real-time PCR. Genomic DNA sequencing was performed to detect BRAF mutation in PTC tumors. The association between UNC5D expression and clinicopathological data from PTC patients was reviewed retrospectively. PTC-derived cancer cell lines TPC-1 and K1 with stable transfection of UNC5D were used to investigate the functions of UNC5D. Flow cytometry, CCK-8, Transwell assay and scratch tests were used to examine cell cycle distribution, proliferation and migration.
Results:
The expression of UNC5D was significantly decreased in PTC compared with adjacent normal thyroid tissues. Lower UNC5D expression was significantly associated with aggressive tumor behaviors, such as lymph node metastasis and BRAF mutation. Overexpression of UNC5D significantly suppressed malignant cell behaviors, including cell proliferation and migration, as well as tumor growth in vivo.
Conclusions:
These findings suggest a potential tumor suppressor role of UNC5D in PTC progression; and provide insight into potential clinical relevance for the prognosis of PTC.
Insights
The UNC5D gene shows reduced expression in papillary thyroid carcinoma (PTC), suggesting it acts as a tumor suppressor. Lower UNC5D levels correlate with aggressive PTC features and impaired tumor growth.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The UNC5D gene has been linked to various cancers, including kidney, bladder, and neuroblastoma.
- Its role in papillary thyroid carcinoma (PTC) has not been fully elucidated.
Purpose of the Study:
- To investigate the potential tumor suppressor function of the UNC5D gene in papillary thyroid carcinoma (PTC).
- To explore the association between UNC5D expression and PTC clinicopathological features.
Main Methods:
- Real-time PCR and DNA sequencing were used to analyze UNC5D mRNA and BRAF mutations in 112 PTC tumors and matched normal tissues.
- In vitro assays (flow cytometry, CCK-8, Transwell, scratch tests) and in vivo studies were conducted using PTC cell lines with UNC5D overexpression.
- Retrospective analysis correlated UNC5D expression with patient clinicopathological data.
Main Results:
- UNC5D mRNA expression was significantly downregulated in PTC tissues compared to normal thyroid tissues.
- Reduced UNC5D expression correlated with advanced tumor characteristics, including lymph node metastasis and BRAF mutations.
- Overexpression of UNC5D inhibited proliferation, migration, and in vivo tumor growth of PTC cells.
Conclusions:
- UNC5D exhibits a tumor suppressor role in papillary thyroid carcinoma progression.
- UNC5D may serve as a potential biomarker for predicting PTC prognosis.
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