Characterization of the novel tumor-suppressor gene CCDC67 in papillary thyroid carcinoma
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De-Tao Yin1,2,*, Jianhui Xu1,2,*, Mengyuan Lei1,2, Hongqiang Li1,2, Yongfei Wang1,2, Zhen Liu1,2, Yubing Zhou3, Mingzhao Xing4
1Department of Thyroid Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, P. R. China
2Key Discipline Laboratory of Clinical Medicine Henan, Zhengzhou 450052, P. R. China
3Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, P. R. China
4Division of Endocrinology and Metabolism, the Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
*These authors contributed equally to this work
De-tao Yin, e-mail: [email protected]
Mingzhao Xing, e-mail: [email protected]
Keywords: thyroid cancer, CCDC67, tumor suppressor, prognostic marker, molecular pathogenesis
Received: September 01, 2015 Accepted: November 25, 2015 Published: December 21, 2015
Background: Some studies showed an association of coiled-coil domain-containing (CCDC) genes with cancers. Our previous limited data specifically suggested a possible pathogenic role of CCDC67 in papillary thyroid cancer (PTC), but this has not been firmly established. The present study was to further investigate and establish this role of CCDC67 in PTC.
Results: The expression of CCDC67, both at mRNA and protein levels, was sharply down-regulated in PTC compared with normal thyroid tissues. Lower CCDC67 expression was significantly associated with aggressive tumor behaviors, such as advanced tumor stages and lymph node metastasis, as well as BRAF mutation. Introduced expression of CCDC67 in TPC-1 cells robustly inhibited cell proliferation, colony formation and migration, induced G1 phase cell cycle arrest, and increased cell apoptosis.
Methods: Primary PTC tumors and matched normal thyroid tissues were obtained from 200 unselected patients at the initial surgery for detection of CCDC67 mRNA and protein by RT-PCR and Western blotting analyses, respectively. Genomic DNA sequencing was performed to detect BRAF mutation in PTC tumors. Clinicopathological data were retrospectively reviewed for correlation analyses. PTC cell line TPC-1 with stable transfection of CCDC67 was used to investigate the functions of CCDC67.
Conclusions: This large study demonstrates down-regulation of CCDC67 in PTC, an inverse relationship between CCDC67 expression and PTC aggressiveness and BRAF mutation, and a robust inhibitory effect of CCDC67 on PTC cellular activities. These results are consistent with CCDC67 being a novel and impaired tumor suppressor gene in PTC, providing important prognostic and therapeutic implications for this cancer.
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