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miR-138-5p和miR-200b-3p在睾丸生殖细胞肿瘤中的功能作用:对精原细胞瘤和畸胎瘤发病机制的分子见解

Functional Role of miR-138-5p and miR-200b-3p in Testicular Germ Cell Tumors: Molecular Insights into Seminoma and Teratoma Pathogenesis.

作者信息

Hooshiar Fatemeh, Azizi Hossein, Masoudi Mahla, Skutella Thomas

机构信息

Department of Stem Cells and Cancer, College of Biotechnology, Amol University of Special Modern Technologies, Amol 46158-63111, Iran.

Institute for Anatomy and Cell Biology, Medical Faculty, University of Heidelberg, Im Neuenheimer Feld 307, 69120 Heidelberg, Germany.

出版信息

Int J Mol Sci. 2025 Aug 21;26(16):8107. doi: 10.3390/ijms26168107.

Abstract

This study aims to investigate the molecular mechanisms underlying germ cell tumors (GCTs), focusing specifically on seminomas and teratomas. By analyzing gene expression profiles and miRNA interactions, the goal is to identify key regulatory miRNAs and signaling pathways that differentiate these tumor types and could serve as important regulators for therapy development. Raw data for seminomas and teratomas were extracted from the GEO database, and gene hubs were identified using STRING and Gephi. Signaling pathways and functional annotations were analyzed using miRPathDB, while miRNA-gene interactions were explored via miRWalk. Hub miRNAs were filtered and confirmed using miRDB. This study highlights significant changes in gene expression diversity between tumor and normal gonadal tissues, providing insights into the molecular dynamics of seminomas and teratomas. Distinctions between seminomas and teratomas were identified, shifting the focus toward miRNAs to discover more precise and novel therapeutic approaches. The hub genes of seminomas and teratomas were identified separately. MiRNAs targeting these hub genes were also determined and confirmed. These miRNAs collectively influence essential oncogenic pathways-confirming hsa-miR-138-5p as a regulator of pathways such as Hippo signaling, transcriptional misregulation in cancer, and microRNA cancer signaling in seminomas, and hsa-miR-200b-3p as a regulator of p53 signaling, T cell receptor signaling, and pathways including PI3K/AKT, MAPK/ERK, and Wnt/β-catenin in teratomas-confirming their potential as promising candidates for subtype-specific therapeutic intervention. MiRNAs identified through bioinformatics analyses, and their predicted regulatory roles in key oncogenic pathways, represent potential therapeutic targets or regulators of biological processes. However, further experimental validation is needed to confirm these findings.

摘要

本研究旨在探究生殖细胞肿瘤(GCTs)潜在的分子机制,特别聚焦于精原细胞瘤和畸胎瘤。通过分析基因表达谱和微小RNA(miRNA)相互作用,目标是识别区分这些肿瘤类型的关键调控miRNA和信号通路,这些通路可作为治疗开发的重要调控因子。从基因表达综合数据库(GEO数据库)中提取精原细胞瘤和畸胎瘤的原始数据,并使用STRING和Gephi软件识别基因枢纽。使用miRPathDB分析信号通路和功能注释,同时通过miRWalk探索miRNA-基因相互作用。使用miRDB对枢纽miRNA进行筛选和确认。本研究突出了肿瘤组织与正常性腺组织之间基因表达多样性的显著变化,为精原细胞瘤和畸胎瘤的分子动力学提供了见解。明确了精原细胞瘤和畸胎瘤之间的差异,将研究重点转向miRNA,以发现更精确和新颖的治疗方法。分别识别了精原细胞瘤和畸胎瘤的枢纽基因。还确定并确认了靶向这些枢纽基因的miRNA。这些miRNA共同影响重要的致癌通路——证实hsa-miR-138-5p是精原细胞瘤中Hippo信号通路、癌症转录失调以及miRNA癌症信号通路等的调控因子,而hsa-miR-200b-3p是畸胎瘤中p53信号通路、T细胞受体信号通路以及包括PI3K/AKT、MAPK/ERK和Wnt/β-连环蛋白等通路的调控因子——证实它们作为亚型特异性治疗干预的有前景候选者的潜力。通过生物信息学分析鉴定的miRNA及其在关键致癌通路中的预测调控作用,代表了潜在的治疗靶点或生物过程的调控因子。然而,需要进一步的实验验证来证实这些发现。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25a3/12386904/245a41a11a88/ijms-26-08107-g001.jpg

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