Tumor-suppressive function of UNC5D in papillary thyroid cancer
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Man-Man Zhang1,*, Feng Sun1,*, Bing Cui2,*, Le-Le Zhang1, Ya Fang1, Yan Li1, Rui-Jia Zhang1, Xiao-Ping Ye1, Yu-Ru Ma1, Bing Han1 and Huai-Dong Song1
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
2Department of Transfusion, The Hospital Affiliated to Jiangsu University, Zhenjiang 212001, China
*These authors should be regarded as joint first authors
Huai-Dong Song, email: [email protected]
Bing Han, email: [email protected]
Keywords: UNC5D; papillary thyroid carcinoma; tumor-suppressive function; lymph node metastasis; BRAF mutation
Received: March 31, 2017 Accepted: June 28, 2017 Published: October 10, 2017
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.
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