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- Title
SIRT6/HIF-1α axis promotes papillary thyroid cancer progression by inducing epithelial–mesenchymal transition.
- Authors
Yang, Zhou; Yu, Weiping; Huang, Renhong; Ye, Min; Min, Zhijun
- 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.
- Subjects
THYROID cancer; CANCER invasiveness; EPITHELIAL tumors; MESENCHYMAL stem cells; SIRTUINS
- Publication
Cancer Cell International, 2019, Vol 19, Issue 1, pN.PAG
- ISSN
1475-2867
- Publication type
Article
- DOI
10.1186/s12935-019-0730-4