Identification of Versican as a target gene of the transcription Factor ZNF587B in ovarian cancer

IF 5.6 2区医学 Q1 PHARMACOLOGY & PHARMACY Biochemical pharmacology Pub Date : 2025-07-01 Epub Date: 2025-04-12 DOI:10.1016/j.bcp.2025.116946

Lu Zhou , Mengke Cui , Jian Yu , Yujie Liu , Feiyue Zeng , Yingzi Liu

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Abstract

Ovarian cancer is the most lethal malignancy affecting the female reproductive system, with its progression and metastasis being significant contributors to patient mortality. Our previous study identified the zinc finger protein ZNF587B as a potential tumor suppressor that inhibited the proliferation, migration and invasion of ovarian cancer cells, although the underlying mechanism remains elusive. In this study, ZNF587B was demonstrated to bind directly to the promoter region of Versican (VCAN), a high molecular weight chondroitin sulfate glycoprotein, and repress its transcription using Chromatin immunoprecipitation-qPCR (ChIP-qPCR), luciferase reporter assays, and immunofluorescence (IF). Moreover, in vivo and in vitro assays revealed that the effect of ZNF587B knockdown on ovarian cancer proliferation may be mediated through VCAN. Not only that, patients with reduced expression of ZNF587B and increased expression of VCAN exhibit a poorer prognosis. The potential mechanism behind this may involve its impact on the phosphorylation process of AKT.

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卵巢癌转录因子ZNF587B靶基因Versican的鉴定

卵巢癌是影响女性生殖系统的最致命的恶性肿瘤，其进展和转移是导致患者死亡的重要因素。我们之前的研究发现锌指蛋白ZNF587B是一种潜在的肿瘤抑制因子，可抑制卵巢癌细胞的增殖、迁移和侵袭，但其潜在机制尚不明确。在本研究中，ZNF587B通过染色质免疫沉淀- qpcr （ChIP-qPCR）、荧光素酶报告基因检测和免疫荧光（IF）证明了它可以直接结合到高分子量硫酸软骨素糖蛋白Versican （VCAN）的启动子区域，并抑制其转录。此外，体内和体外实验表明，ZNF587B基因敲低对卵巢癌增殖的影响可能是通过VCAN介导的。不仅如此，ZNF587B表达降低、VCAN表达升高的患者预后更差。其潜在机制可能涉及其对AKT磷酸化过程的影响。

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来源期刊

Biochemical pharmacology 医学-药学

CiteScore

10.30

自引率

1.70%

发文量

420

审稿时长

17 days

期刊介绍： Biochemical Pharmacology publishes original research findings, Commentaries and review articles related to the elucidation of cellular and tissue function(s) at the biochemical and molecular levels, the modification of cellular phenotype(s) by genetic, transcriptional/translational or drug/compound-induced modifications, as well as the pharmacodynamics and pharmacokinetics of xenobiotics and drugs, the latter including both small molecules and biologics. The journal''s target audience includes scientists engaged in the identification and study of the mechanisms of action of xenobiotics, biologics and drugs and in the drug discovery and development process. All areas of cellular biology and cellular, tissue/organ and whole animal pharmacology fall within the scope of the journal. Drug classes covered include anti-infectives, anti-inflammatory agents, chemotherapeutics, cardiovascular, endocrinological, immunological, metabolic, neurological and psychiatric drugs, as well as research on drug metabolism and kinetics. While medicinal chemistry is a topic of complimentary interest, manuscripts in this area must contain sufficient biological data to characterize pharmacologically the compounds reported. Submissions describing work focused predominately on chemical synthesis and molecular modeling will not be considered for review. While particular emphasis is placed on reporting the results of molecular and biochemical studies, research involving the use of tissue and animal models of human pathophysiology and toxicology is of interest to the extent that it helps define drug mechanisms of action, safety and efficacy.