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miR-221/222 通过激活 Akt 通路促进神经胶质瘤的恶性进展。

miR-221/222 promote malignant progression of glioma through activation of the Akt pathway.

机构信息

Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, P.R. China.

出版信息

Int J Oncol. 2010 Apr;36(4):913-20. doi: 10.3892/ijo_00000570.

Abstract

MicroRNAs (miRNAs) are short regulatory RNAs that negatively modulate protein expression at a post-transcriptional level. Emerging evidence suggests that miRNAs play important roles in the pathogenesis of several types of cancers. However, the further mechanisms of miRNA remain unknown. In this study, we aimed to explore the coordinated function of miR-221/222 in glioma by bioinformatics and experiment methods. Bioinformatics analysis revealed that miR-221/222 had the potential to regulate about 70 common target genes and may exert a cooperative effect on regulation and function via Akt signaling pathway. Overexpression of miR-221/222 increased glioma cell proliferation and invasion in vitro and induced glioma growth in a subcutaneous mouse model. Furthermore, miR-221/222 overexpression resulted in an obvious activation of p-Akt and significant changes of Akt-related gene expression in glioma cells. Our results suggest that miR-221/222 co-enhance the glioma malignant phenotype via activation of the Akt pathway mediated by regulation of common gene expression.

摘要

微小 RNA(miRNAs)是一种短的调控 RNA,可在转录后水平负调控蛋白质表达。越来越多的证据表明,miRNAs 在多种类型癌症的发病机制中发挥着重要作用。然而,miRNA 的进一步机制尚不清楚。在这项研究中,我们旨在通过生物信息学和实验方法来探讨 miR-221/222 在神经胶质瘤中的协同作用。生物信息学分析表明,miR-221/222 可能调节约 70 个共同的靶基因,并可能通过 Akt 信号通路对调节和功能发挥协同作用。miR-221/222 的过表达可增加体外神经胶质瘤细胞的增殖和侵袭,并诱导皮下小鼠模型中的神经胶质瘤生长。此外,miR-221/222 的过表达导致 Akt 相关基因表达的明显激活和 Akt 通路的显著改变。我们的研究结果表明,miR-221/222 通过调节共同基因表达介导的 Akt 通路的激活来共同增强神经胶质瘤的恶性表型。

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