HDAC2 promotes malignant progression by the RBM47/NONO axis in medulloblastoma

IF 5 2区医学 Q2 Medicine

Translational Oncology Pub Date : 2025-09-29 DOI:10.1016/j.tranon.2025.102549

Houji Song , Siyu Zhang , Jie Chen , Gaichao Zhao , Fujing Wei , Jingjie Zhou , Tianxiang Feng , Hui Zhao , Ping Liang , Hongjuan Cui

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引用次数: 0

Abstract

Background

Medulloblastoma (MB) is one of the most prevalent pediatric brain tumors, constituting approximately 20 % of all childhood brain malignancies. The modification of histone acetylation is recognized for its significance in tumor growth and survival. However, its role in MB has been scarcely investigated. Here, we demonstrate that the Histone deacetylase 2 (HDAC2) modulates oncogene expression and promotes tumorigenesis in MB tumors.

Methods

To elucidate the biological roles of HDAC2 in MB, we employed lentivirus-mediated RNA interference (RNAi) to deplete HDAC2. Subsequently, we employed EdU, flow cytometry (FCM), Transwell assay, and cell line-derived xenograft (CDX) models to evaluate the effects of HDAC2 on proliferation, migration and invasion of MB cells. The underlying mechanism of HDAC2 in MB was further investigated using qRT-PCR, Western blot, CHIP-qPCR, and Luciferase reporter assays.

Results

We found that HDAC2 is overexpressed in both MB patient tissues and MB cell lines. The knockdown of HDAC2 significantly inhibited the proliferation, migration, and invasion abilities of MB cells. Mechanistically, HDAC2 promoted RBM47 expression through H3K27 deacetylation. The expression of NONO was increased in MB cells overexpressing RBM47. Critically, HDAC2 knockdown enhanced the sensitivity of MB cells to temozolomide treatment.

Conclusions

Our results suggest that HDAC2 plays an oncogenic role in MB. Targeting the HDAC2/RBM47/NONO axis could be a potential therapeutic strategy for MB patients.

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HDAC2通过RBM47/NONO轴促进髓母细胞瘤的恶性进展。

背景：髓母细胞瘤（MB）是最常见的儿童脑肿瘤之一，约占所有儿童脑恶性肿瘤的20%。组蛋白乙酰化修饰在肿瘤生长和生存中具有重要意义。然而，其在MB中的作用很少被研究。在这里，我们证明了组蛋白去乙酰化酶2 （HDAC2）在MB肿瘤中调节癌基因表达并促进肿瘤发生。方法：为了阐明HDAC2在MB中的生物学作用，我们采用慢病毒介导的RNA干扰（RNAi）来清除HDAC2。随后，我们采用EdU、流式细胞术（FCM）、Transwell实验和细胞系来源的异种移植（CDX）模型来评估HDAC2对MB细胞增殖、迁移和侵袭的影响。通过qRT-PCR、Western blot、CHIP-qPCR和荧光素酶报告基因检测进一步研究HDAC2在MB中的潜在机制。结果：我们发现HDAC2在MB患者组织和MB细胞系中均过表达。HDAC2基因的表达下调可显著抑制MB细胞的增殖、迁移和侵袭能力。机制上，HDAC2通过H3K27去乙酰化促进RBM47表达。NONO在过表达RBM47的MB细胞中表达增加。关键的是，HDAC2敲低增强了MB细胞对替莫唑胺治疗的敏感性。结论：我们的研究结果表明HDAC2在MB中起致瘤作用，靶向HDAC2/RBM47/NONO轴可能是MB患者的潜在治疗策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Translational Oncology ONCOLOGY-

CiteScore

8.40

自引率

2.00%

发文量

314

审稿时长

54 days

期刊介绍： Translational Oncology publishes the results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of oncology patients. Translational Oncology will publish laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer. Peer reviewed manuscript types include Original Reports, Reviews and Editorials.