SAT-123 Nuclear Receptor 4A1 (NR4A1) Acts as a Tumor Suppressor in Anaplastic Thyroid Cancer

The nuclear orphan receptor NR4A1 has been demonstrated to play important roles in development and progression of various cancers. However, the biological roles and its underlying mechanisms of NR4A1 in anaplastic thyroid cancer (ATC) are largely unknown. Here, we showed that the expression level of NR4A1 was robustly down-regulated in ATC cell lines and human ATC tissues as compared to Nthy-ori 3-1 cells and normal thyroid tissues, respectively, using in silico analysis, qRT-PCR and immunohistochemistry analyses. Gain-of-function experiments were carried out to understand the NR4A1’s responsiveness to apoptotic inducers. The results showed that ectopic over-expression of NR4A1 reduced cell viability and promoted cell apoptotic rate induced by UV irradiation or Adriamycin. Moreover, the activities of caspase-3 and PARP were elevated in NR4A1 overexpression cells in response to apoptotic inducers. Furthermore, we found that down-regulation of XIPA was involved in the pro-apoptotic role of NR4A1 in ATC cells. Collectively, these findings suggest that the nuclear orphan receptor NR4A1 acts as a tumor suppressor in ATC via regulating XIPA, providing a potential therapeutic target against ATC.