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

• Main Authors: Zhou Yang, Weiping Yu, Renhong Huang, Min Ye, Zhijun Min
• Format: Article
• Language: English
• Published: BMC 2019-01-01
• Series: Cancer Cell International
• Subjects: Sirtuin 6; Hypoxia inducible factor-1α; Papillary thyroid cancer; Epithelial–mesenchymal transition; Sirtuins
• Online Access: http://link.springer.com/article/10.1186/s12935-019-0730-4

Abstract Background In 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-1α (HIF-1α). Methods SIRT6-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-1α expression was further detected by western blotting in both normoxia and hypoxia conditions. A HIF-1α inhibitor was then used to block HIF-1α expression in SIRT6-upregulated PTC cells. The same parameters were then assessed and compared with control HIF-1α cells. Results E-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-1α 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-1α expression. Furthermore, we found that SIRT6 increased PTC resistance to HIF-1α inhibitor-mediated proliferation changes. Conclusion These results confirm that the SIRT6/HIF-1α axis promotes papillary thyroid cancer progression by inducing EMT.