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微小RNA-577通过Wnt信号通路抑制胶质母细胞瘤的肿瘤生长。

miR-577 inhibits glioblastoma tumor growth via the Wnt signaling pathway.

作者信息

Zhang Weiguang, Shen Chen, Li Chenguang, Yang Guang, Liu Huailei, Chen Xin, Zhu Dan, Zou Huichao, Zhen Yunbo, Zhang Daming, Zhao Shiguang

机构信息

Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China.

Institute of Brain Science, Harbin Medical University, Harbin, Heilongjiang Province, China.

出版信息

Mol Carcinog. 2016 May;55(5):575-85. doi: 10.1002/mc.22304. Epub 2015 Mar 12.

Abstract

microRNAs (miRNAs) are commonly altered in glioblastoma. Publicly available algorithms suggest the Wnt pathway is a potential target of miR-577 and the Wnt pathway is commonly altered in glioblastoma. Glioblastoma has not been previously evaluated for miR-577 expression. Glioblastoma tumors and cell lines were evaluated for their expression of miR-577. Cell lines were transfected with miR-577, miR-577-mutant, or control mimics to evaluate the effect of miR-577 expression on cell proliferation in vitro and in an animal model. Wnt pathway markers were also evaluated for their association with miR-577 expression. miR-577 expression was decreased in 33 of 40 (82.5%) glioblastoma tumors and 5 of 6 glioblastoma cell lines. miR-577 expression correlated negatively with cell growth and cell viability. miR-577 down-regulation was associated with increased expression of the Wnt signaling pathway genes lipoprotein receptor-related protein (LRP) 6 (LRP6) and β-catenin. Western blot analysis confirmed decreased expression of the Wnt signaling pathway genes Axin2, c-myc, and cyclin D1 in miR-577 transfected cells. miR-577 expression is down-regulated in glioblastoma. miR-577 directly targets Wnt signaling pathway components LRP6 and β-catenin. miR-577 suppresses glioblastoma multiforme (GBM) growth by regulating the Wnt signaling pathway.

摘要

微小RNA(miRNA)在胶质母细胞瘤中通常会发生改变。公开可用的算法表明,Wnt信号通路是miR-577的潜在靶点,且Wnt信号通路在胶质母细胞瘤中通常会发生改变。此前尚未对胶质母细胞瘤中的miR-577表达进行评估。对胶质母细胞瘤肿瘤和细胞系进行miR-577表达评估。用miR-577、miR-577突变体或对照模拟物转染细胞系,以评估miR-577表达对体外和动物模型中细胞增殖的影响。还评估了Wnt信号通路标志物与miR-577表达的相关性。40例胶质母细胞瘤肿瘤中有33例(82.5%)以及6个胶质母细胞瘤细胞系中有5个的miR-577表达降低。miR-577表达与细胞生长和细胞活力呈负相关。miR-577下调与Wnt信号通路基因脂蛋白受体相关蛋白(LRP)6(LRP6)和β-连环蛋白的表达增加有关。蛋白质印迹分析证实,在转染miR-577的细胞中,Wnt信号通路基因Axin2、c-myc和细胞周期蛋白D1的表达降低。胶质母细胞瘤中miR-577表达下调。miR-577直接靶向Wnt信号通路成分LRP6和β-连环蛋白。miR-577通过调节Wnt信号通路抑制多形性胶质母细胞瘤(GBM)的生长。

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