SIRT6/HIF-1α axis promotes papillary thyroid cancer progression by inducing epithelial-mesenchymal transition

BackgroundIn our previous study, we demonstrated that Sirtuin 6 (SIRT6) is upregulated and associated with papillary thyroid cancer (PTC) progression (Qu et al. in Int J Oncol 50(5):1683-92, 2017). This study examined whether SIRT6 promotes epithelial-mesenchymal transition (EMT) of papillary thyroid cancer through hypoxia inducible factor-1 (HIF-1).MethodsSIRT6-upregulated TPC-1 and B-CPAP cells were generated by lentivirus. Western blotting, RT-qPCR, immunofluorescence was performed to detect the following EMT associated markers: E-cadherin, Vimentin, Snail, and TWIST. Cell proliferation was detected by CCK8, and cell invasion and migration were detected by transwell and wound healing assays, respectively. HIF-1 expression was further detected by western blotting in both normoxia and hypoxia conditions. A HIF-1 inhibitor was then used to block HIF-1 expression in SIRT6-upregulated PTC cells. The same parameters were then assessed and compared with control HIF-1 cells.ResultsE-cadherin was significantly decreased, whereas Vimentin, Snail, and TWIST were increased in SIRT6-upregulated PTC cells. Additionally, SIRT6 promoted the invasion and migration of PTC cells. We found that SIRT6 enhanced HIF-1 stability and synthesis and prolonged the protein half-life. The changes in the EMT associated markers and in the invasion and migration ability were rescued after inhibition of HIF-1 expression. Furthermore, we found that SIRT6 increased PTC resistance to HIF-1 inhibitor-mediated proliferation changes.ConclusionThese results confirm that the SIRT6/HIF-1 axis promotes papillary thyroid cancer progression by inducing EMT.