The miRNA Content of Exosomes Released from the Glioma Microenvironment Can Affect Malignant Progression.

The miRNA Content of Exosomes Released from the Glioma Microenvironment Can Affect Malignant Progression.
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DOI:
10.3390/biomedicines8120564
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发表时间:
2020-12-03
期刊:
影响因子:
4.7
通讯作者:
Cesselli D
Cesselli D
中科院分区:
工程技术3区
文献类型:
--
作者:
Caponnetto F;Dalla E;Mangoni D;Piazza S;Radovic S;Ius T;Skrap M;Di Loreto C;Beltrami AP;Manini I;Cesselli D

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低级别胶质瘤 (LGG) 是浸润性原发性脑肿瘤,70% 的病例会发生间变性转化,严重影响预后。然而,进展的时间是异质的。近年来,肿瘤微环境(TME)作为预后因素或治疗靶点受到了广泛关注。通过释放细胞外囊泡,TME 通过转移 microRNA 等生物活性分子来促进肿瘤进展。该研究的目的是利用神经胶质瘤相关干细胞(GASC)(一种具有预后意义的神经胶质瘤微环境体外模型)及其释放的外泌体,研究外泌体 miRNA 在促进 LGG 间变性转化中的可能作用。因此,通过深度测序,我们分析并比较了不同预后的LGG患者的GASC和外泌体的miRNA谱。结果表明,与细胞对应物相比,外泌体呈现出不同的特征,并且尽管共享多个 miRNA,但预后不良患者的外泌体选择性表达了一些可能导致更具侵袭性表型的 miRNA。这些发现深入了解了 TME 和外泌体作为旨在改善 LGG 预后分层和治疗策略的精准医学方法的潜在生物标志物的价值。
Low-grade gliomas (LGG) are infiltrative primary brain tumors that in 70% of the cases undergo anaplastic transformation, deeply affecting prognosis. However, the timing of progression is heterogeneous. Recently, the tumor microenvironment (TME) has gained much attention either as prognostic factor or therapeutic target. Through the release of extracellular vesicles, the TME contributes to tumor progression by transferring bioactive molecules such as microRNA. The aim of the study was to take advantage of glioma-associated stem cells (GASC), an in vitro model of the glioma microenvironment endowed with a prognostic significance, and their released exosomes, to investigate the possible role of exosome miRNAs in favoring the anaplastic transformation of LGG. Therefore, by deep sequencing, we analyzed and compared the miRNA profile of GASC and exosomes obtained from LGG patients characterized by different prognosis. Results showed that exosomes presented a different signature, when compared to their cellular counterpart and that, although sharing several miRNAs, exosomes of patients with a bad prognosis, selectively expressed some miRNAs possibly responsible for the more aggressive phenotype. These findings get insights into the value of TME and exosomes as potential biomarkers for precision medicine approaches aimed at improving LGG prognostic stratification and therapeutic strategies.
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