ZNF677 Suppresses Akt Phosphorylation and Tumorigenesis in Thyroid Cancer

Cancer Research
Yujun LiPeng Hou

Abstract

The zinc finger protein 677 (ZNF677) belongs to the zinc finger protein family, which possesses transcription factor activity by binding sequence-specific DNA. Previous studies have reported its downregulated by promoter methylation in non-small cell lung cancer. However, its biological role and exact mechanism in human cancers, including thyroid cancer, remain unknown. In this study, we demonstrate that ZNF677 is frequently downregulated by promoter methylation in primary papillary thyroid cancers (PTC) and show that decreased expression of ZNF677 is significantly associated with poor patient survival. Ectopic expression of ZNF677 in thyroid cancer cells dramatically inhibited cell proliferation, colony formation, migration, invasion, and tumorigenic potential in nude mice and induced cell-cycle arrest and apoptosis. Conversely, knockdown of ZNF677 promoted thyroid cancer cell proliferation and colony formation. ZNF677 exerted its tumor suppressor functions in thyroid cancer cells through transcriptional repression of two targets CDKN3 and HSPB1 (or HSP27), thereby inhibiting phosphorylation and activation of Akt via distinct mechanisms. Taken together, our data show that ZNF677 functions as a tumor suppressor and is frequentl...Continue Reading

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Citations

Aug 14, 2020·BMC Bioinformatics·Bihai ZhaoLei Wang
May 1, 2021·International Journal of Molecular Sciences·Letizia PaladinoFrancesca Rappa
Jun 26, 2021·Experimental and Molecular Pathology·Negar BidarBehzad Baradaran
Aug 8, 2021·International Journal of Molecular Sciences·Abdul K SirajKhawla S Al-Kuraya

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