Background
Papillary thyroid cancer (PTC) is one of the malignant tumors with rapidly increasing morbidity and mortality. Sirtuin 7 (SIRT7) is a desuccinylase that is involved in tumorigenesis. The activation of large tumor suppressor 1 (LATS1) can effectively suppress tumorigenesis in multiple tumors and can be affected by SIRT7. This study aimed to explore the role and mechanism of SIRT7 in PTC progression.
Conclusion
Taken together, silencing of SIRT7 promotes the succinylation of LATS1 to enhance LATS1 stability, thus inhibiting the progression of PTC. Therefore, SIRT7 and LATS1 may become novel and potential therapeutic targets for PTC.
Methods
The RNA and protein levels were detected by quantitative real-time PCR (qPCR) and western blot, respectively. Cell proliferation was measured by cell counting kit-8 and colony formation. The apoptosis of PTC cells was analyzed by flow cytometry and Live/dead cell staining. The interaction between proteins was detected by co-immunoprecipitation.
Results
The results showed that SIRT7 was highly expressed in PTC tissues and cells. Functional studies showed that knockdown of SIRT7 inhibited the proliferation and induced apoptosis of PTC cells. Mechanistically, SIRT7 could directly interact with LATS1 and reduce the stability of the LATS1 protein. Later, rescue experiments suggested that LATS1 silencing reversed the effect of SIRT7 knockdown on PTC cell growth and apoptosis. In addition, SIRT7 promoted tumor growth in vivo.