Mediator complex subunit 16 is down-regulated in papillary thyroid cancer, leading to increased transforming growth factor-β signaling and radioiodine resistance.

Mediator complex subunit 16 (MED16) is a component of the mediator complex and functions as a coactivator in transcriptional events at almost all RNA polymerase II-dependent genes. In this study, we report that the expression of MED16 is markedly decreased in papillary thyroid cancer (PTC) tumors compared with normal thyroid tissues. In vitro, MED16 overexpression in PTC cells significantly inhibited cell migration, enhanced sodium/iodide symporter expression and iodine uptake, and decreased resistance to radioactive 131I (RAI). Conversely, PTC cells in which MED16 had been further knocked down (MED16KD) exhibited enhanced cell migration, epithelial-mesenchymal transition, and RAI resistance, accompanied by decreased sodium/iodide symporter levels. Moreover, cell signaling through transforming growth factor β (TGF-β) was highly activated after the MED16 knockdown. Similar results were obtained in MED12KD PTC cells, and a co-immunoprecipitation experiment verified interactions between MED16 and MED12 and between MED16 and TGF-βR2. Of note, the application of LY2157299, a potent inhibitor of TGF-β signaling, significantly attenuated MED16KD-induced RAI resistance both in vitro and in vivo In conclusion, our findings indicate that MED16 reduction in PTC contributes to tumor progression and RAI resistance via the activation of the TGF-β pathway. © 2020 Gao et al.

Citation

Hongwei Gao, Peirong Bai, Lin Xiao, Mengjia Shen, Qiuxiao Yu, Yuanyuan Lei, Wenting Huang, Xiang Lin, Xinyi Zheng, Tao Wei, Yong Jiang, Feng Ye, Hong Bu. Mediator complex subunit 16 is down-regulated in papillary thyroid cancer, leading to increased transforming growth factor-β signaling and radioiodine resistance. The Journal of biological chemistry. 2020 Jul 31;295(31):10726-10740

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PMID: 32532820

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