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解析多形性胶质母细胞瘤中独特且常见的细胞类型特异性机制。

Unraveling unique and common cell type-specific mechanisms in glioblastoma multiforme.

作者信息

Fathima Samreen, Sinha Swati, Donakonda Sainitin

机构信息

Department of Biotechnology, Faculty of Life and Allied Health Sciences, MS Ramaiah University of Applied Sciences, Bangalore, India.

Institute of Molecular Immunology and Experimental Oncology, Klinikum Rechts Der Isar, Technical University of Munich, Munich, Germany.

出版信息

Comput Struct Biotechnol J. 2021 Dec 9;20:90-106. doi: 10.1016/j.csbj.2021.12.010. eCollection 2022.

Abstract

Glioblastoma multiforme persists to be an enigmatic distress in neuro-oncology. Its untethering capacity to thrive in a confined microenvironment, metastasize intracranially, and remain resistant to the systemic treatments, renders this tumour incurable. The glial cell type specificity in GBM remains exploratory. In our study, we aimed to address this problem by studying the GBM at the cell type level in the brain. The cellular makeup of this tumour is composed of genetically altered glial cells which include astrocyte, microglia, oligodendrocyte precursor cell, newly formed oligodendrocyte and myelinating oligodendrocyte. We extracted cell type-specific solid tumour as well as recurrent solid tumour glioma genes, and studied their functional networks and contribution towards gliomagenesis. We identified the principal transcription factors that are found to be regulating vital tumorigenic processes. We also assessed the protein-protein interaction networks at their domain level to get a more microscopic view of the structural and functional operations that transpire in these cells. This yielded the eminent protein regulators exhibiting their regulation in signaling pathways. Overall, our study unveiled regulatory mechanisms in glioma cell types that can be targeted for a more efficient glioma therapy.

摘要

多形性胶质母细胞瘤仍然是神经肿瘤学中一个难以捉摸的难题。它在有限的微环境中生长、在颅内转移以及对全身治疗保持耐药的能力,使得这种肿瘤无法治愈。胶质母细胞瘤中胶质细胞类型的特异性仍在探索之中。在我们的研究中,我们旨在通过在大脑的细胞类型水平上研究胶质母细胞瘤来解决这个问题。这种肿瘤的细胞组成由基因改变的胶质细胞组成,包括星形胶质细胞、小胶质细胞、少突胶质前体细胞、新形成的少突胶质细胞和有髓鞘的少突胶质细胞。我们提取了细胞类型特异性的实体瘤以及复发性实体瘤胶质瘤基因,并研究了它们的功能网络以及对胶质瘤发生的贡献。我们确定了发现调控重要致瘤过程的主要转录因子。我们还在其结构域水平评估了蛋白质-蛋白质相互作用网络,以更微观地了解这些细胞中发生的结构和功能运作。这产生了在信号通路中表现出调控作用的重要蛋白质调节因子。总体而言,我们的研究揭示了胶质瘤细胞类型中的调控机制,这些机制可作为更有效治疗胶质瘤的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e954/8688884/4239eea0e93c/ga1.jpg

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