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.
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.