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Coordination of FOXA2 and SIRT6 suppresses the hepatocellular carcinoma progression through ZEB2 inhibition

Authors Liu J, Yu Z, Xiao Y, Meng Q, Wang Y, Chang W

Received 1 September 2017

Accepted for publication 27 November 2017

Published 1 March 2018 Volume 2018:10 Pages 391—402

DOI https://doi.org/10.2147/CMAR.S150552

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Dr Kenan Onel


Jinghua Liu,1 Zhen Yu,2 Yuanyuan Xiao,2 Qiong Meng,2 Yeying Wang,2 Wei Chang2

1Department of Gastroenterology and Hepatology, The 4th Affiliated Hospital of Kunming Medical University, 2School of Public Health, Kunming Medical University, Kunming, China

Background: The Forkhead transcription family member FOXA2 plays a fundamental role in hepatocellular carcinoma (HCC) progression, but the precise interaction factor and molecular regulation of FOXA2 are not fully understood.
Objective: In this study, we found that FOXA2 could interact with sirtuin 6 (SIRT6) directly in vivo and in vitro. We explored that the expressions of FOXA2 and SIRT6 were significantly downregulated in human HCC and HCC cell lines.
Methods: Functionally, cell counting kit-8 assay and Transwell® assay were performed; we demonstrated that the knockdown of FOXA2 and SIRT6 promoted HepG2 cells and Huh7 cells proliferation and invasion in vitro.
Results: Mechanically, using luciferase reporter assay and fast chromatin immunoprecipitation assay, we showed that FOXA2 and SIRT6 regulated the expression of ZEB2 from transcription level. ZEB2 suppression was involved in the anti-oncogenesis effect of FOXA2 and SIRT6. The negative correlation between the expressions of ZEB2 and FOXA2 or SIRT6 was observed in the tissues of HCC patients.
Conclusion: Our findings indicated that the coordination function of FOXA2 and SIRT6 played a critical role in HCC progression and may serve as potential drug candidates for HCC.

Keywords: FOXA2, SIRT6, ZEB2, proliferation, invasion

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