Downregulation of SIRT7 inhibits the biological characteristics of OC cells.

SIRT7 regulates acetylation of GATA4 to inhibit transcriptional activity of GATA4.

GATA4 induces OC cell senescence by inhibiting Wnt signaling pathway.

SIRT7 inhibits GATA4 transcription to promote growth of OC.

This study provides a potential target for the treatment of OC.

Sirtuin-7 (SIRT7) is a class III histone deacetylase that plays an important role in cancer development and frequently overexpressed in carcinomas. In this study, the tumor-supporting role and underlying mechanisms of SIRT7 were characterized in ovarian cancer (OC) aggressiveness.

SIRT7 expression was examined in OC tissues and cells. Interactions among SIRT7, GATA4, Wnt signaling pathway were explored by bioinformatics tools and experimental validations. The effect of SIRT7 and GATA4 on malignant phenotypes of OC cells were examined with gain- and loss-of-function experiments. A nude mouse model of OC was developed to verify the in vitro findings.

It was noted that SIRT7 was highly expressed in OC tissues and cells. Cell lines with higher SIRT7 expression (OVCAR-3 and OVCAR-8) were used for subsequent in vitro experiments. The experimental data indicated that silencing of SIRT7 suppressed the OC cell proliferation, colony formation, migration, and invasion, and promoted cell senescence, which could be abolished by GATA4 knockdown. Mechanistically, SIRT7 promoted deacetylation of GATA4 and consequently inhibited the transcriptional activity of GATA4. In addition, GATA4 induced OC cell senescence by inhibiting Wnt signaling pathway. Further in vivo experiments substantiated that SIRT7 knockdown or overexpressed GATA4 could effectively inhibit tumor growth of nude mice.

Taken together, our findings indicated that SIRT7 enhanced development of OC by suppressing GATA4 and activating Wnt signaling pathway, suggesting the potential of SIRT7/GATA4/Wnt axis as a therapeutic target for OC.

Ovarian cancer

SIRT7

GATA4

Transcriptional activity

Deacetylation

Wnt signaling pathway

Cell senescence

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