Abstract
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Objectives Although recent studies have shown that the expression of miR125a-5p is downregulated in several human cancers such as breast cancer, ovarian cancer, lung cancer, and medulloblastoma, its specific roles in thyroid cancer cell is still unknown. To study its function, we examined the effects of hsa-miR-125a-5p in anaplastic thyroid cancer cells cancer cells.
Methods Real time RT-PCR was used to evaluate miR-125a-5p expression in nine undifferentiated and seven differentiated papillary thyroid cancer cases with distant metastases. The regulation of P53 by miR-125a-5p was examined with Ad-miR-125a-5p infection. Furthermore, we investigated whether miR-125a-5p enhances radioiodine therapy effect of anaplastic thyroid cancer cells in combination with Ad-Sur-NIS, a recombinant adenovirus that expressed the NIS gene under control of the survivin promoter.
Results Real-time PCR showed that miR-125a-5p in undifferentiated PTC cancer tissue was only 1/43.8 of that in differentiated PTC (P=0.010,Figure 1A). In gain-of-function experiments on human anaplastic thyroid carcinoma cells (ARO) expressing mutant p53 (mt-p53) through recombinant adenoviral vectors (Ad-miR-125a-5p) infection, P53 protein level was significantly upregulated. Synchronous with the P53 change upon artificial miR145 overexpression, ARO cells showed increased cell death as assayed by flow cytometry (from 5.1% to 18.2%,Figure 1B). When Ad-Sur-NIS and Ad-miR-125a-5p were transduced to ARO cells, the survival rate of cells incubated with I-131 (74 MBq) decreased to 32%±17.8% ,In contrast, the survival rate of ARO cells transduced with Ad-Sur-NIS was 64%±25.4%(Figure 1C).
Conclusions In this study, we showed that miR-125a-5p functions as a crucial tumor suppressor in human thyroid cancer. It could induce ARO cells apoptosis via a p53-dependent pathway. Overexpression of miR-125a-5p enhanced the radioiodine cytotoxic effect when coinfection with Ad-Sur-NIS.