文章：

弥漫性大B细胞淋巴瘤中G9a高表达及其通过氯硝柳胺抑制诱导自噬作为治疗策略

High G9a Expression in DLBCL and Its Inhibition by Niclosamide to Induce Autophagy as a Therapeutic Approach

原文发布日期：17 August 2023

DOI: 10.3390/cancers15164150

类型: Article

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英文摘要：

Background: Diffuse large B-cell lymphoma (DLBCL) is a malignant lymphoid tumor disease that is characterized by heterogeneity, but current treatment does not benefit all patients, which highlights the need to identify oncogenic genes and appropriate drugs. G9a is a histone methyltransferase that catalyzes histone H3 lysine 9 (H3K9) methylation to regulate gene function and expression in various cancers. Methods: TCGA and GTEx data were analyzed using the GEPIA2 platform. Cell viability under drug treatment was assessed using Alamar Blue reagent; the interaction between G9a and niclosamide was assessed using molecular docking analysis; mRNA and protein expression were quantified in DLBCL cell lines. Finally, G9a expression was quantified in 39 DLBCL patient samples. Results: The TCGA database analysis revealed higher G9a mRNA expression in DLBCL compared to normal tissues. Niclosamide inhibited DLBCL cell line proliferation in a time- and dose-dependent manner, reducing G9a expression and increasing p62, BECN1, and LC3 gene expression by autophagy pathway regulation. There was a correlation between G9a expression in DLBCL samples and clinical data, showing that advanced cancer stages exhibited a higher proportion of G9a-expressing cells. Conclusion: G9a overexpression is associated with tumor progression in DLBCL. Niclosamide effectively inhibits DLBCL growth by reducing G9a expression via the cellular autophagy pathway; therefore, G9a is a potential molecular target for the development of therapeutic strategies for DLBCL.

摘要翻译： 

背景：弥漫性大B细胞淋巴瘤（DLBCL）是一种具有异质性的恶性淋巴肿瘤疾病，但现有治疗方案无法使所有患者获益，这凸显了识别致癌基因及相应治疗药物的必要性。G9a作为一种组蛋白甲基转移酶，可通过催化组蛋白H3第9位赖氨酸（H3K9）甲基化，在多种癌症中调控基因功能与表达。方法：通过GEPIA2平台分析TCGA与GTEx数据库数据；使用Alamar Blue试剂检测药物处理下的细胞活力；采用分子对接分析评估G9a与氯硝柳胺的相互作用；在DLBCL细胞系中定量检测mRNA及蛋白表达水平；最终对39例DLBCL患者样本进行G9a表达定量分析。结果：TCGA数据库分析显示DLBCL组织中G9a mRNA表达水平显著高于正常组织。氯硝柳胺能以时间和剂量依赖性方式抑制DLBCL细胞系增殖，通过调控自噬通路降低G9a表达，同时提升p62、BECN1和LC3基因表达水平。DLBCL样本中G9a表达与临床数据存在相关性，晚期癌症分期样本中G9a阳性细胞比例更高。结论：G9a过表达与DLBCL肿瘤进展相关。氯硝柳胺通过细胞自噬通路降低G9a表达，从而有效抑制DLBCL生长，因此G9a可作为DLBCL治疗策略开发的潜在分子靶点。

原文链接：

High G9a Expression in DLBCL and Its Inhibition by Niclosamide to Induce Autophagy as a Therapeutic Approach