Abstract
Purpose
Thyroid cancer is the most common endocrine malignancy worldwide. The molecular mechanisms underlying thyroid tumorigenesis remain unclear. Some studies suggested that the ZCCHC12 gene correlates with certain diseases. However, the function of ZCCHC12 in thyroid cancer has yet to be determined. This study investigated the role of the ZCCHC12 gene in papillary thyroid cancer (PTC).
Methods
We conducted a comprehensive analysis of massively parallel whole-transcriptome resequencing of matched PTC tumors and normal tissues in 19 patients. Results showed that the expression of ZCCHC12 was significantly upregulated in thyroid cancer. qRT-PCR was performed to confirm previous results. The functions of the ZCCHC12 gene in PTC cell lines (TPC1 and BCPAP) transfected with small interfering RNA were determined through cell colony formation assay, migration assay, and invasion assay.
Results
The ZCCHC12 gene was remarkably upregulated in primary PTC tumors in both validated cohort (T:N = 1.80 ± 2.58:0.23 ± 0.50, P < 0.01) and TCGA cohort (T:N = 7.63 ± 3.25:1.55 ± 1.71, P < 0.01). We also achieved area under the curve (AUC of ROC) of 87.9% for the validated cohort while 91.4% for the TCGA cohort to classify PTC tumors and normal tissues. ZCCHC12 overexpression correlated with lymph node metastasis in both cohorts (P < 0.05). In in vitro experiments, ZCCHC12 downregulation significantly inhibited the colony formation, migration, and invasion of PTC cells.
Conclusion
Our study indicated that ZCCHC12 gene has important biological functions and acts as a metastasis-related oncogene in PTC.
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Acknowledgements
This work was supported by a Grant from the Major Science and Technology Projects of Zhejiang Province (2015C03052), Wenzhou Science and Technology Planning Project (Y20160126), and Scientific Research Incubator Project of The First Affiliated Hospital of Wenzhou Medical University (No. FHY2014018).
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Ethical approval for this study was obtained from the Ethnic Committee of the First Affiliated Hospital of Wenzhou Medical University.
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Written informed consent was obtained from each individual participant.
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Wang, O., Zheng, Z., Wang, Q. et al. ZCCHC12, a novel oncogene in papillary thyroid cancer. J Cancer Res Clin Oncol 143, 1679–1686 (2017). https://doi.org/10.1007/s00432-017-2414-6
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DOI: https://doi.org/10.1007/s00432-017-2414-6