Sirtuin 7（SIRT7）是一种癌基因，可促进多种恶性肿瘤的肿瘤进展，然而，其在宫颈鳞状细胞癌（CSCC）中的作用和调节机制尚不清楚。在此，我们试图研究 SIRT7 在 CSCC 进展中的功能作用和分子机制。使用各种测定法评估 CSCC 细胞中 SIRT7 的表达。然后，我们使用一系列功能增益和损失实验来确定 SIRT7 在 CSCC 进展中的作用。此外，还进行了机制实验来评估 SIRT7/USP39/FOXM1 在 CSCC 细胞中的相互作用。此外，还进行了救援实验，以探索 USP39/FOXM1 在 CSCC 细胞过程中的调节功能。SIRT7 在 CSCC 患者组织和细胞系中高表达。 SIRT7 缺陷对体外 CSCC 细胞的增殖和自噬以及体内肿瘤发生具有显着抑制作用。同样，SIRT7 敲低后，CSCC 细胞的凋亡和 ROS 产生加速。此外，SIRT7 和 USP39 被发现共定位于细胞核中。有趣的是，SIRT7 可以使 USP39 去乙酰化，从而促进其在 CSCC 细胞中的蛋白质稳定性。 USP39 蛋白也被证实在 CSCC 组织和细胞中表达上调。 USP39 沉默对 CSCC 细胞生长有抑制作用。从机制上讲，USP39 通过促进 FOXM1 的转录活性来上调 SIRT7。救援实验还表明，SIRT7通过调节USP39/FOXM1促进CSCC细胞自噬并抑制ROS产生。SIRT7/USP39/FOXM1正反馈网络调节CSCC中的自噬和氧化应激，从而为CSCC靶向治疗提供新方向。© 2023。作者。

Sirtuin 7 (SIRT7) is an oncogene that promotes tumor progression in various malignancies, however, its role and regulatory mechanism in cervical squamous cell carcinoma (CSCC) is unknown. Herein, we attempted to investigate the functional role and molecular mechanism of SIRT7 underlying CSCC progression.SIRT7 expression was evaluated in CSCC cells using various assays. We then used a series of function gain-and-loss experiments to determine the role of SIRT7 in CSCC progression. Furthermore, mechanism experiments were conducted to assess the interaction between SIRT7/USP39/FOXM1 in CSCC cells. Additionally, rescue assays were conducted to explore the regulatory function of USP39/FOXM1 in CSCC cellular processes.SIRT7 was highly expressed in CSCC patient tissues and cell lines. SIRT7 deficiency showed significant repression on the proliferation, and autophagy of CSCC cells in vitro and tumorigenesis in vivo. Similarly, apoptosis and ROS production in CSCC cells were accelerated after the SIRT7 knockdown. Moreover, SIRT7 and USP39 were found colocalized in the cell nucleus. Interestingly, SIRT7 was revealed to deacetylate USP39 to promote its protein stability in CSCC cells. USP39 protein was also verified to be upregulated in CSCC tissues and cells. USP39 silencing showed suppressive effects on CSCC cell growth. Mechanistically, USP39 was revealed to upregulate SIRT7 by promoting the transcriptional activity of FOXM1. Rescue assays also indicated that SIRT7 promoted autophagy and inhibited ROS production in CSCC cells by regulating USP39/FOXM1.The SIRT7/USP39/FOXM1 positive feedback network regulates autophagy and oxidative stress in CSCC, thus providing a new direction for CSCC-targeted therapy.© 2023. The Author(s).