Glioblastoma with PRMT5 gene upregulation is a key target for tumor cell regression

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Accounts of Chemical Research Pub Date : 2024-01-23 DOI:10.1515/oncologie-2023-0534

Maher Kurdi, Motaz M Fadul, Bassam J. Addas, Eyad Faizo, Ahmed K. Bamaga, Taghreed A. Alsinani, Yousef Katib, Alaa Alkhotani, Amany A Fathaddin, Alaa N. Turkistani, Ahmed A. Najjar, Saleh Baeesa, Fadi A. Toonsi, Majid Almansouri, Shadi Alkhayyat

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Abstract

Protein Arginine Methyltransferase 5 (PRMT5) is an enzyme that regulates gene expression and protein function through arginine methylation. Its association with isocitrate dehydrogenase (IDH) mutation in Grade-4 astrocytoma was rarely investigated. Our aim was to aim to explore the association between IDH mutation and PRMT5 and its effect on tumor recurrence. A retrospective cohort of 34 patients with Grade 4 astrocytoma has been tested for PRMT5 expression using protein and gene expression arrays. The impact of IDH-mutation and PRMT5 expression on tumor recurrence was explored. IDH-wildtype was detected in 13 tumors. PRMT5 protein was highly expressed in 30 tumors and the expression was low in four tumors. PRMT5 gene expression was upregulated in 33 tumors and downregulated in a single tumor case. Tumors with different PRMT5 gene expressions and IDH mutation were found to have a significant statistical difference in recurrence-free interval (RFI) (p-value<0.001). IDH-wildtype glioblastoma with upregulated PRMT5 gene or protein expression showed earlier tumor recurrence compared to IDH-mutant Grade 4 astrocytoma with upregulated PRMT5 expression. The association between IDH mutation and PRMT5 in IDH-mutant Grade 4 astrocytoma or IDH-wildtype glioblastoma is indirectly bidirectional. PRMT5 upregulation in glioblastoma can lead to increased cell proliferation and tumor regrowth.

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胶质母细胞瘤 PRMT5 基因上调是肿瘤细胞消退的关键靶点

蛋白精氨酸甲基转移酶 5（PRMT5）是一种通过精氨酸甲基化调节基因表达和蛋白质功能的酶。在4级星形细胞瘤中，它与异柠檬酸脱氢酶（IDH）突变的关系很少被研究。我们的目的是探讨 IDH 突变与 PRMT5 之间的关联及其对肿瘤复发的影响。我们使用蛋白质和基因表达阵列对 34 例 4 级星形细胞瘤患者进行了 PRMT5 表达的回顾性队列检测。研究还探讨了IDH突变和PRMT5表达对肿瘤复发的影响。在 13 个肿瘤中检测到 IDH-野生型。30 例肿瘤中 PRMT5 蛋白高表达，4 例肿瘤中 PRMT5 蛋白低表达。33 例肿瘤的 PRMT5 基因表达上调，1 例肿瘤的 PRMT5 基因表达下调。研究发现，PRMT5基因表达和IDH突变不同的肿瘤，其无复发间隔（RFI）有显著统计学差异（P值<0.001）。PRMT5基因或蛋白表达上调的IDH野生型胶质母细胞瘤与PRMT5表达上调的IDH突变4级星形细胞瘤相比，肿瘤复发时间更早。在IDH突变的4级星形细胞瘤或IDH野生型胶质母细胞瘤中，IDH突变与PRMT5之间的关系是间接双向的。胶质母细胞瘤中 PRMT5 的上调可导致细胞增殖和肿瘤再生。

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

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.