NOL7 Inhibits Ovarian Cancer Progression and Suppresses Angiogenesis by Stabilizing GADD45A to Deactivate STAT3

Sep 22, 2026

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Ovarian cancer drives global morbidity through dysregulated proliferation and angiogenesis. Nucleolar Protein 7 (NOL7), an RNA-binding tumor suppressor, is linked to anti-angiogenic activity, yet its ovarian mechanisms are unclear. This study shows NOL7 is down-regulated in ovarian tumors and correlates with worse patient prognosis. NOL7 overexpression reduces viability, suppresses cell cycle entry and proliferation, promotes apoptosis, lowers VEGF-A, raises TSP-1, and blocks angiogenesis in vitro. Knockdown enhances growth and angiogenesis. In vivo, NOL7 restrains tumor growth by stabilizing GADD45A mRNA and deactivating STAT3 Ser727 phosphorylation, supporting NOL7/GADD45A as a therapeutic target.

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CategoryHealthcare

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Introduction

NOL7 and ovarian cancer background

GADD45A roles and angiogenesis regulation

Cancer Science ORIGINAL ARTICLE OPEN ACCESS Carcinogenesis NOL7 Inhibits Ovarian Cancer Progression and Suppresses Angiogenesis by Stabilizing GADD45A to Deactivate STAT3 Xinyu Xu1,2 | Jiayuan Wang3 | Meng Jiang4 | Ling Ouyang2 1Department of Obstetrics, Dalian Women and Children's Medical Group, Dalian, China | 2Department of Gynecology, Shengjing Hospital of China Medical University, Shenyang, China | 3Department of Reproductive Medicine, Dalian Women and Children's Medical Group, Dalian, China | 4Department of Gynecology, Dalian Women and Children's Medical Group, Dalian, China Correspondence: Ling Ouyang ([stone10243@126.com](stone10243@126.com)) Received: 28 September 2025 | Revised: 12 February 2026 | Accepted: 20 February 2026 Keywords: angiogenesis | GADD45A | NOL7 | ovarian cancer | tumor growth ABSTRACT Ovarian cancer is one of the most prevalent gynecologic malignancies worldwide. Dysregulated cell proliferation and angiogenesis are well-recognized to be involved in the pathogenesis of ovarian cancer. Nucleolar Protein 7 (NOL7), a novel RNA-binding protein, has been identified as a tumor suppressor and a key anti-angiogenetic factor. However, the function of NOL7 and its underlying molecular mechanisms in ovarian cancer remain unclear. In this study, we demonstrated that NOL7 expression was down-regulated in ovarian cancer tissues, and low NOL7 expression was associated with poorer prognosis in patients with ovarian cancer. Overexpression of NOL7 decreased cell viability, inhibited cell cycle entry and proliferation, and promoted apoptosis in OVCAR-3 and SKOV-3 cells. Additionally, NOL7 overexpression decreased VEGF-A level, increased TSP-1, and suppressed angiogenesis of human umbilical vein endothelial cells (HUVECs) . Conversely, knockdown of NOL7 in ovarian cancer cells enhanced cell proliferation and angiogenesis, while reducing apoptosis. In vivo experiments further confirmed that NOL7 overexpression inhibited tumor growth and angiogenesis. Mechanistic studies revealed that NOL7 could bind to the 3′UTR of growth arrest and DNA damage inducible alpha (GADD45A), and overexpression of NOL7 up-regulated GADD45A expression by stabilizing GADD45A mRNA in ovarian cancer cells. The anti-cancer effects of the NOL7/GADD45A were mediated by inhibiting the phosphorylation of STAT3 at Ser727. Collectively, our findings indicate that NOL7 functions as a tumor suppressor in ovarian cancer and provide a novel therapeutic target for the treatment of ovarian cancer. 1 | Introduction Ovarian cancer is the fifth leading cause of cancer-related deaths in women and has the highest mortality rate among all gynecologic malignancies [1, 2] . Early-stage ovarian cancer is typically asymptomatic, and no effective screening strategies are currently available in clinical practice. Consequently, most patients are diagnosed at an advanced stage, with a 5-year overall survival rate as low as 30%, making ovarian cancer a severe global threat to women's health [3]. Therefore, there is an urgent imperative to explore novel therapeutic targets for improving the clinical treatment efficacy of ovarian cancer. The nucleolar Protein 7 (NOL7) gene is located on chromosome 6p23, a genomic region frequently subjected to loss of heterozygosity in various cancers [4, 5] . NOL7 encodes amultifunctional nuclear protein that exists as multiple splice variants with distinct biological characteristics. NOL7's nucleolar localization is tightly associated with the maintenance of nucleolar structural homeostasis and the regulation of cell | Abbreviations: GADD45A, growth arrest and DNA damage inducible alpha; HUVECs, human umbilical vein endothelial cells; mRNA-seq, mRNA-sequencing; NLSs, nuclear localization sequences; NOL7, nucleolar protein 7; RIP-seq, RNA-binding protein immunoprecipitation sequencing; TSP-1, thrombospondin-1. | | --- | | This is an open access article under the terms of the Creative Commons Attribution-NonC

FAQs

How does NOL7 affect ovarian cancer cell growth and survival?

NOL7 overexpression decreases cell viability, inhibits cell cycle entry and proliferation, and promotes apoptosis in ovarian cancer cells. NOL7 knockdown produces the opposite effects, enhancing proliferation and angiogenesis while reducing apoptosis.

What angiogenesis changes are associated with NOL7 activity?

NOL7 overexpression decreases VEGF-A levels, increases TSP-1, and suppresses angiogenesis of HUVECs. Conversely, NOL7 knockdown enhances angiogenesis.

What mechanism links NOL7 to STAT3 deactivation in ovarian cancer?

NOL7 binds the 3′UTR of GADD45A and stabilizes GADD45A mRNA, increasing GADD45A expression. The anti-cancer effects are mediated by inhibiting phosphorylation of STAT3 at Ser727, corresponding with reduced tumor growth and angiogenesis.

Sep 22, 2026

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