Downregulation of NONO Suppresses Proliferation, Migration, and Invasion in Metastatic Prostate Cancer.

IF 2.6 3区 医学 Q3 ENDOCRINOLOGY & METABOLISM
Prostate Pub Date : 2025-06-12 DOI:10.1002/pros.24925
Anna-Lena Lemster, Sarah Grünhagen, Sarah Schmalfeld, Florian Lenz, Anna Natzius, Anne Offermann, Sven Perner, Jiong Zhang, Verena Sailer, Jutta Kirfel
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引用次数: 0

Abstract

Background: As prostate cancer (PCa) remains one of the leading causes of cancer-related death in men, it is important to develop effective therapeutic approaches for the treatment of metastatic PCa and to improve the accuracy of prognosis for aggressive tumors. Non-POU domain-containing octamer-binding (NONO) is involved in RNA transport and almost all steps of gene regulation, and aberrant expression is associated with tumorigenesis in various tumor entities.

Methods: Immunohistochemical analysis of the expression of NONO was performed in a cohort of 405 patient samples, including 54 benign prostate tissues, 250 primary prostate tumors, and 101 metastatic tissue samples. To assess the role of NONO in PCa cells, siRNA-mediated knockdown of NONO in the metastatic PCa cell lines PC3 and DU145, followed by a series of functional assays including proliferation, transwell, western blotting, and real-time quantitative PCR, was used.

Results: The current study showed that the nuclear expression of NONO increases during the progression of PCa and is highest in distant metastases. NONO regulates cell proliferation by increasing the expression of cell cycle-related genes. In addition, NONO modulates migration and invasion in PCa cells.

Conclusion: Overall, these results suggest inhibition of NONO may be a promising approach for the treatment of metastatic PCa.

NONO的下调抑制转移性前列腺癌的增殖、迁移和侵袭。
背景:由于前列腺癌(PCa)仍然是男性癌症相关死亡的主要原因之一,因此开发有效的治疗方法来治疗转移性前列腺癌和提高侵袭性肿瘤预后的准确性非常重要。非pou结构域的八聚体结合(NONO)参与RNA转运和基因调控的几乎所有步骤,并且在各种肿瘤实体中异常表达与肿瘤发生有关。方法:对405例患者样本进行NONO表达的免疫组化分析,其中包括54例良性前列腺组织,250例原发性前列腺肿瘤和101例转移组织样本。为了评估NONO在PCa细胞中的作用,研究人员在转移性PCa细胞系PC3和DU145中使用sirna介导的NONO敲低,随后进行了一系列功能分析,包括增殖、transwell、western blotting和实时定量PCR。结果:目前的研究表明,NONO的核表达在前列腺癌的进展过程中增加,并在远处转移中最高。NONO通过增加细胞周期相关基因的表达来调节细胞增殖。此外,NONO还调节前列腺癌细胞的迁移和侵袭。结论:总的来说,这些结果表明抑制NONO可能是治疗转移性前列腺癌的一种有希望的方法。
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来源期刊
Prostate
Prostate 医学-泌尿学与肾脏学
CiteScore
5.10
自引率
3.60%
发文量
180
审稿时长
1.5 months
期刊介绍: The Prostate is a peer-reviewed journal dedicated to original studies of this organ and the male accessory glands. It serves as an international medium for these studies, presenting comprehensive coverage of clinical, anatomic, embryologic, physiologic, endocrinologic, and biochemical studies.
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