miR-129-5p targets Wnt5a to block PKC/ERK/NF-κB and JNK pathways in glioblastoma.
miR-129-5p targets Wnt5a to block PKC/ERK/NF-κB and JNK pathways in glioblastoma.
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miR-129-5p 靶向 Wnt5a，阻断胶质母细胞瘤中的 PKC/ERK/NF-kappaB 和 JNK 通路。
DOI：
10.1038/s41419-018-0343-1
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发表时间：
2018-03-12
影响因子：
9
通讯作者：
You Y
中科院分区：
文献类型：
--
作者：
Zeng A;Yin J;Li Y;Li R;Wang Z;Zhou X;Jin X;Shen F;Yan W;You Y
MicroRNAs(MiRNAs)在Wnt驱动的胶质瘤中的治疗应用已经很有价值，但其具体的作用和机制还没有完全被研究。采用实时定量聚合酶链式反应(RT-qPCR)分析microRNA-129-5p(miR-129-5p)在人脑胶质瘤组织中的表达。应用细胞计数试剂盒8(CCK-8)、流式细胞仪、EDU、血管生成、Transwell侵袭、伤口愈合、体外三维迁移和神经球形成实验检测miR-129-5p在多形性胶质母细胞瘤(GBM)细胞中的作用。此外，我们还进行了荧光素酶报告实验和RNA芯片(染色质免疫沉淀)实验，以确定Wnt5a是否是miR-129-5p的直接靶点。我们还从中国胶质瘤基因组图谱(CGGA)中证实了miR-129-5p和Wnt5a在胶质瘤患者中的表达谱之间的相关性，并根据Wnt5a的表达情况，使用TCGA和GSE16011两个数据集调查了GBM患者的总体生存情况。在CGGA胶质瘤患者中，MIR-129-5p的表达水平下调，并与Wnt5a的表达水平呈负相关。MiR-129-5p的恢复表达阻断了GBM细胞的增殖、侵袭、迁移、血管生成、神经球的形成和对替莫唑胺的耐药性。我们报道了miR-129-5p在胶质瘤中直接靶向Wnt5a。此外，我们还观察到，miR-129-5p的过表达抑制了Wnt5a的表达，从而阻断了蛋白激酶C/ERK/NF-κB和JNK通路。抑制Wnt5a可以挽救miR-129-5p缺失的影响，而Wnt5a表达增加与GBM患者的总存活率降低有关。我们还利用体内模型证明了miR-129-5P对GBM肿瘤生长的抑制作用。MiR-129-5p/Wnt5a-Axis介导的PKC/ERK/NF-κB和JNKB通路具有治疗基底膜的潜力。
Therapeutic application of microRNAs (miRNAs) in Wnt-driven glioma has been valuable; however, their specific roles and mechanisms have not been completely investigated. Real-time quantitative PCR (RT-qPCR) was used to analyse the expression of microRNA-129-5p (miR-129-5p) in human glioma samples. Cell-Counting Kit 8 (CCK-8), flow cytometry, EdU, angiogenesis, Transwell invasion, wound healing, in vitro 3D migration and neurosphere formation assays were employed to assess the role of miR-129-5p in glioblastoma multiforme (GBM) cells. Moreover, we performed the luciferase reporter assay and the RNA-ChIP (chromatin immunoprecipitation) assay to confirm whether Wnt5a was a direct target of miR-129-5p. We also confirmed the correlation between the expression profile of miR-129-5p and Wnt5a in glioma patients from the Chinese Glioma Genome Atlas (CGGA) and investigated the overall survival of GBM patients using two data sets, namely, TCGA and GSE16011, according to their Wnt5a expression status. MiR-129-5p expression levels were downregulated and inversely correlated with Wnt5a expression levels in CGGA glioma patients. Restored expression of miR-129-5p blocked GBM cell proliferation, invasion, migration, angiogenesis, neurosphere formation and resistance to temozolomide. We reported that miR-129-5p directly targeted Wnt5a in glioma. Furthermore, we observed that overexpression of miR-129-5p inhibited the expression of Wnt5a, thus blocking the protein kinase C(PKC)/ERK/NF-κB and JNK pathways. Inhibiting Wnt5a rescued the effects of miR-129-5p loss and increased Wnt5a expression was associated with reduced overall survival of GBM patients. We also demonstrated the inhibitory effect of miR-129-5p on tumour growth in GBM using an in vivo model. The miR-129-5p/Wnt5a-axis-mediated PKC/ERK/NF-κB and JNK pathways have therapeutic potential in GBM treatment.
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影响因子：
37.3
作者：
Beier D;Schulz JB;Beier CP
通讯作者：
Beier CP
272 例胶质瘤的 RNA 测序揭示了继发性胶质母细胞瘤中一种新的、复发性 PTPRZ1-MET 融合转录本。
影响因子：
7
作者：
Bao ZS;Chen HM;Yang MY;Zhang CB;Yu K;Ye WL;Hu BQ;Yan W;Zhang W;Akers J;Ramakrishnan V;Li J;Carter B;Liu YW;Hu HM;Wang Z;Li MY;Yao K;Qiu XG;Kang CS;You YP;Fan XL;Song WS;Li RQ;Su XD;Chen CC;Jiang T
通讯作者：
Jiang T
DOI：
10.1073/pnas.0712148105
发表时间：
2008-02-26
影响因子：
11.1
作者：
Fukuda, Tetsuya;Chen, Liguang;Kipps, Thomas J.
通讯作者：
Kipps, Thomas J.
DOI：
10.1073/pnas.1221478110
发表时间：
2013-05-21
影响因子：
11.1
作者：
Mao, Ping;Joshi, Kaushal;Nakano, Ichiro
通讯作者：
Nakano, Ichiro
影响因子：
4.7
作者：
Lucon DR;Rocha Cde S;Craveiro RB;Dilloo D;Cardinalli IA;Cavalcanti DP;Aguiar Sdos S;Maurer-Morelli C;Yunes JA
通讯作者：
Yunes JA