The Clinical Significance And Function Study Of ZNRF3 In Papillary Thyroid Carcinoma

OBJECTIVEIn recent years,with the increasing incidence rate of thyroid cancer,it has become the most common tumor in endocrine system.In this study,the expression of ZNRF3 would be detected in thyroid cancer and para-thyroid cancer,combined with the clinical data of sample cases,the correlation of clinical and ZNRF3 expression data was elucidated.To study the effects ZNRF3 gene on proliferation and invasion of thyroid cancer cells,lentivirus was syntheticed to infect and improve the expression of ZNRF3 in thyroid carcinoma cell line TPC-1 and K1.Combined with the expression of WNT signaling pathway related protein(β-catenin and TCF4),We first discovered the mechanism that how ZNRF3 worked in thyroid cancer development.It provides a new reference index for the pathological diagnosis and prognostic clinical cases,and prompted a new site for the targeted treatment of thyroid cancer.MATERIALS AND METHODS132 pairs of thyroid tumor samples were collected from thyroid cancer surgery.qPCR,immunohistochemistry and western blotting were performed to measure the expression of ZNRF3,β-catenin and TCF4 in thyroid cancer specimens and adjacent normal tissues;Packaging lentivirus with pEGFP-ZNRF3 recombinant plasmids(or empty plasmids as control).The lentivirus was used to the over-expression of wild-type ZNRF3,which was accomplished by the transient transfection of lentivirus into the cell line K1 and TPC1.The results was confirmed by western blot analysis;Cell Counting Kit-8 assays and transwell were used to exam the ability if prolife,invasion and migration with ZNRF3 overexpressed;western blot analysis was used to detecte the component beta-catenin and TCF-4 in WNT singling.Finally,30 nude mices were divided into two groups to establish subcutaneous tumor model.Immunohistochemical was performed to detect the expression of Ki-67 in subcutaneous tumors,to determine the impact ZNRF3 tumorigenic capacity on thyroid tumors.RESULTThe expression of ZNRF3 in thyroid cancer tissues was significantly lower than corresponding adjacent tissues.And there is a significant relationship between ZNRF3 expression and TNM stage,lymph node metastasis.Overexpression of ZNRF3 in TPC-1 and K-1 inhibited the proliferation and promoting cell invasion and metastasis in thyroid cancer cells.ZNRF3 was functioned in thyroid cancer through WNT signaling pathway.In vivo,ZNRF3 can inhibit the formation and proliferation of thyroid tumor significantly.CONCLUSIONZNRF3 is a tumor suppressor gene in the development of thyroid cancer.We found that ZNRF3 inhibited thyroid tumor mainly through the WNT signaling pathway.