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表征人类髓母细胞瘤干细胞的微小RNA-蛋白质组网络

MicroRNAs-Proteomic Networks Characterizing Human Medulloblastoma-SLCs.

作者信息

Catanzaro Giuseppina, Besharat Zein Mersini, Garg Neha, Ronci Maurizio, Pieroni Luisa, Miele Evelina, Mastronuzzi Angela, Carai Andrea, Alfano Vincenzo, Po Agnese, Screpanti Isabella, Locatelli Franco, Urbani Andrea, Ferretti Elisabetta

机构信息

Department of Molecular Medicine and Experimental Medicine, Sapienza University, 00161 Rome, Italy.

Department of Molecular Medicine, Sapienza University, 00161 Rome, Italy.

出版信息

Stem Cells Int. 2016;2016:2683042. doi: 10.1155/2016/2683042. Epub 2016 Jan 6.

Abstract

Medulloblastoma (MB) is the most common malignant brain tumor of pediatric age and is characterized by cells expressing stem, astroglial, and neuronal markers. Among them, stem-like cells (hMB-SLCs) represent a fraction of the tumor cell population with the potential of self-renewal and proliferation and have been associated with tumor poor prognosis. In this context, microRNAs have been described as playing a pivotal role in stem cells differentiation. In our paper, we analyze microRNAs profile and genes expression of hMB-SLCs before and after Retinoic Acid- (RA-) induced differentiation. We aimed to identify pivotal players of specific pathways sustaining stemness and/or tumor development and progression and integrate the results of our recent proteomic study. Our results uncovered 22 differentially expressed microRNAs that were used as input together with deregulated genes and proteins in the Genomatix Pathway System (GePS) analysis revealing 3 subnetworks that could be interestingly involved in the maintenance of hMB-SLCs proliferation. Taken together, our findings highlight microRNAs, genes, and proteins that are significantly modulated in hMB-SLCs with respect to their RA-differentiated counterparts and could open new perspectives for prognostic and therapeutic intervention on MB.

摘要

髓母细胞瘤(MB)是儿童期最常见的恶性脑肿瘤,其特征是细胞表达干细胞、星形胶质细胞和神经元标志物。其中,干细胞样细胞(hMB-SLCs)是肿瘤细胞群体的一部分,具有自我更新和增殖的潜力,并与肿瘤预后不良相关。在这种情况下,微小RNA已被描述为在干细胞分化中起关键作用。在我们的论文中,我们分析了视黄酸(RA)诱导分化前后hMB-SLCs的微小RNA谱和基因表达。我们旨在确定维持干性和/或肿瘤发生发展的特定途径的关键参与者,并整合我们最近蛋白质组学研究的结果。我们的结果发现了22种差异表达的微小RNA,它们与失调的基因和蛋白质一起作为输入,在Genomatix途径系统(GePS)分析中揭示了3个可能有趣地参与维持hMB-SLCs增殖的子网。综上所述,我们的研究结果突出了hMB-SLCs相对于其RA分化对应物显著调节的微小RNA、基因和蛋白质,并可能为MB的预后和治疗干预开辟新的前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97e3/4736593/29e897a5a079/SCI2016-2683042.001.jpg

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