Aim: Thyroid cancer (TC) is the most common malignant tumor of the endocrine system. Studies have showed that Triiodothyronine (T3) promotes the proliferation of papillary thyroid cancer (PTC) cells, but the specific mechanism remains unclear. Several studies have showed that PDZK1 played important roles in the occurrence and development of cancer. However, the biological function of PDZK1 in PTC remains unclear. Therefore, the aims of this study were to investigate the effect of PDZK1 in PTC

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... d the underlying mechanism.Materials and Methods: The effect of T3 on proliferation of PTC cell (TPC-1) was analyzed by colony formation assay and real time cell analysis. Immunofluorescence staining aimed to analyze protein expression. RNA-seq was used to analyze the expression of PDZK1. Meanwhile, Western blot was used to verify the protein expression. The effect of PDZK1 on PTC cell proliferation was investigated by Cell Counting Kit-8(CCK8), real time cell analysis, flow cytometry and transwell assay, respectively. Results: We found that T3 increased the expression of PDZK1 in TPC-1 cells and promote the proliferation of TPC-1 cells which can be weakened after PDZK1 was knocked down. Immunofluorescence staining showed that the expression of PDZK1 was higher in PTC than paracancerous tissues. And the analysis of 6 benign thyroid nodules and 4 thyroid cancer tissues by RNA-Seq showed that the expression of PDZK1 was increased in PTC tissues, the expression of PDZK1 was also increased in PTC cells compared with the normal thyroid epithelium. In addition, PDZK1 promoted TPC-1 cell proliferation was detected by real-time cell analysis (RTCA) and CCK8. Flow cytometry analysis showed that PDZK1 increased cell cycle at S phase and decreased at G1 phase of TPC-1. PDZK1 promoted the invasion of TPC-1 cell was tested by transwell. Conclusion: These results suggest that T3 can promote the proliferation of PTC cells, which may be mediated by PDZK1. This study illustrates a possible mechanism by which T3 promotes the proliferation of PTC and provides a theoretical basis for the prevention and treatment of PTC.