ELMOD2 Overexpression Predicts Adverse Outcomes and Regulates Tumor Progression in Gliomas.

IF 2 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL
Rui-Chao Li, Chang Liu, Guo-Jian Wang, Zi Wang, Rong-Lin Li, Hao-Tian Lu, Xiao-Xun Xie, Qing-Mei Zhang, Da-Qin Feng, Xiang Yun, Bin Luo
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引用次数: 0

Abstract

Objective: Glioma is a highly heterogeneous and malignant intracranial tumor that presents challenges for clinical treatment. ELMO domain containing 2 (ELMOD2) is a GTPase-activating protein that regulates a range of cellular biological processes. However, its specific role and prognostic value in tumorigenesis are still unknown. This study aimed to assess the prognostic relevance and signaling function of ELMOD2 in gliomas.

Methods: The Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA) databases were utilized to conduct a comprehensive analysis of the expression profile of ELMOD2 in gliomas, elucidating its associations with clinicopathological parameters and patient prognosis. Single-cell analysis was performed to characterize ELMOD2 expression across distinct glioma cell subpopulations. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, and Gene Set Variation Analysis (GSVA) were employed to evaluate the potential biological functions of ELMOD2 in gliomagenesis. Specific small interfering RNAs (siRNAs) were used to knock down ELMOD2 in the glioma cell lines U251 and A172 to assess their cellular behaviors and examine the levels of multiple key signaling molecules associated with the occurrence of gliomas.

Results: ELMOD2 was overexpressed in gliomas, and this upregulation was correlated with tumor grade, isocitrate dehydrogenase mutation, and 1p/19q codeletion status. Notably, ELMOD2 expression was elevated in classical and mesenchymal subtypes, and single-cell resolution analysis revealed predominant enrichment within malignant cells. Functionally, ELMOD2 regulated cell cycle progression, and its overexpression was related to independent adverse outcomes. In vitro experiments revealed that ELMOD2 was located in the cytoplasm and nucleoplasm. Furthermore, ELMOD2 knockdown reduced proliferation, migration, and invasion and increased apoptosis in U251 and A172 cell lines. Finally, ELMOD2 knockdown significantly decreased p-Erk1/2.

Conclusions: ELMOD2 expression in glioma is positively correlated with tumorigenesis and is a crucial independent prognostic marker. Thus, ELMOD2 is a promising biomarker and therapeutic target for glioma treatment.

ELMOD2过表达可预测胶质瘤的不良结局并调节肿瘤进展。
目的:胶质瘤是一种高度异质性的颅内恶性肿瘤,对临床治疗提出了挑战。ELMO结构域2 (ELMOD2)是一种调节一系列细胞生物学过程的gtpase激活蛋白。然而,其在肿瘤发生中的具体作用和预后价值尚不清楚。本研究旨在评估ELMOD2在胶质瘤中的预后相关性和信号功能。方法:利用中国胶质瘤基因组图谱(CGGA)和肿瘤基因组图谱(TCGA)数据库,全面分析ELMOD2在胶质瘤中的表达谱,阐明其与临床病理参数和患者预后的关系。进行单细胞分析以表征ELMOD2在不同胶质瘤细胞亚群中的表达。采用基因本体(GO)、京都基因与基因组百科全书(KEGG)富集分析和基因集变异分析(GSVA)来评估ELMOD2在胶质瘤形成中的潜在生物学功能。使用特异性小干扰rna (sirna)敲低胶质瘤细胞系U251和A172中的ELMOD2,以评估其细胞行为,并检测与胶质瘤发生相关的多种关键信号分子的水平。结果:ELMOD2在胶质瘤中过表达,且这种上调与肿瘤分级、异柠檬酸脱氢酶突变和1p/19q编码状态相关。值得注意的是,ELMOD2在经典亚型和间充质亚型中表达升高,单细胞分辨率分析显示恶性细胞中主要富集。功能上,ELMOD2调节细胞周期进程,其过表达与独立的不良后果相关。体外实验表明,ELMOD2位于细胞质和核质中。此外,ELMOD2敲低可降低U251和A172细胞系的增殖、迁移和侵袭,并增加凋亡。最后,ELMOD2敲除显著降低p-Erk1/2。结论:ELMOD2在胶质瘤中的表达与肿瘤发生呈正相关,是一个重要的独立预后指标。因此,ELMOD2是一种很有前景的生物标志物和胶质瘤治疗靶点。
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
Current Medical Science
Current Medical Science Biochemistry, Genetics and Molecular Biology-Genetics
CiteScore
4.70
自引率
0.00%
发文量
126
期刊介绍: Current Medical Science provides a forum for peer-reviewed papers in the medical sciences, to promote academic exchange between Chinese researchers and doctors and their foreign counterparts. The journal covers the subjects of biomedicine such as physiology, biochemistry, molecular biology, pharmacology, pathology and pathophysiology, etc., and clinical research, such as surgery, internal medicine, obstetrics and gynecology, pediatrics and otorhinolaryngology etc. The articles appearing in Current Medical Science are mainly in English, with a very small number of its papers in German, to pay tribute to its German founder. This journal is the only medical periodical in Western languages sponsored by an educational institution located in the central part of China.
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