Sirtuin-7（SIRT7）是一种第III类组蛋白去乙酰化酶，在癌症发展中扮演重要角色，经常在癌瘤中过度表达。本研究揭示了SIRT7在卵巢癌（OC）恶性程度中的作用和潜在机制。检测了OC组织和细胞中SIRT7的表达情况，并运用生物信息学工具和实验验证探讨了SIRT7、GATA4和Wnt信号通路之间的相互作用关系。通过增减功能实验评估了SIRT7和GATA4对OC细胞恶性表型的影响。基于此，在裸鼠模型中进一步验证了体外实验的结果。 结果表明，OC组织和细胞中高表达SIRT7。接下来，使用表达SIRT7更高的OVCAR-3 和 OVCAR-8 细胞系进行了体外实验，发现抑制SIRT7可显著抑制OC细胞的增殖、形成集落、迁移和侵袭，并促进细胞衰老，这一效应可被GATA4敲除所消除。机制上，SIRT7可促进GATA4去乙酰化，从而抑制其转录活性。另外，GATA4通过抑制Wnt信号通路诱导OC细胞衰老。进一步体内实验验证了SIRT7敲除或高表达GATA4可以有效抑制裸鼠的肿瘤生长。 综上，我们的研究结果表明，SIRT7通过抑制GATA4，激活Wnt信号通路来促进OC发展，并且暗示了SIRT7/GATA4/Wnt轴作为OC治疗靶点的潜力。版权所有©2023 Elsevier Inc.

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.Copyright © 2023 Elsevier Inc. All rights reserved.