miR-29a/b/c function as invasion suppressors for gliomas by targeting CDC42 and predict the prognosis of patients.
miR-29a/b/c function as invasion suppressors for gliomas by targeting CDC42 and predict the prognosis of patients.
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miR-29a/b/c通过靶向CDC42作为胶质瘤的侵袭抑制因子并预测患者的预后
DOI：
10.1038/bjc.2017.255
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发表时间：
2017-09-26
影响因子：
8.8
通讯作者：
Yu S
中科院分区：
文献类型：
--
作者：
Shi C;Ren L;Sun C;Yu L;Bian X;Zhou X;Wen Y;Hua D;Zhao S;Luo W;Wang R;Rao C;Wang Q;Yu S
背景：高级别胶质瘤的致死率和不良预后是肿瘤不断侵袭的结果。 miR-29a/b/c 下调表达导致多种人类肿瘤发生。然而，它们与胶质瘤预后和侵袭的相关性仍不清楚。方法：通过原位杂交和免疫组化分析147例人胶质瘤中miR-29a/b/c和CDC42的表达与分级和生存时间的关系。双荧光素酶报告基因测定用于鉴定 CDC42 作为 miR-29a/b/c 的靶标。通过体外和体内实验研究了 miR-29a/b/c 抑制胶质瘤细胞迁移和侵袭的机制。结果：miR-29a/b/c 表达与胶质瘤分级呈负相关，但与患者生存呈正相关。根据 miR-29a/b/c 表达，鉴定出具有不同预后的 I-IV 级神经胶质瘤患者的两个不同亚组。 miR-29a/b/c 过表达通过靶向 CDC42 并随后减少磷酸化 PAK1/2/3、LIMK1/2 和 cofilin（CDC42 的关键下游效应器）来抑制神经胶质瘤细胞迁移和侵袭。此外，CDC42表达与胶质瘤分级呈正相关，但与miR-29a/b/c表达和患者生存呈负相关。在胶质母细胞瘤细胞系中，CDC42敲低可以模拟miR-29a/b/c的抗肿瘤作用。结论：miR-29a/b/c是重要的肿瘤抑制因子和胶质瘤的新型预后生物标志物，miR-29a/b/c和CDC42是恶性胶质瘤的潜在治疗候选者。
Background:The lethality and poor outcome of high-grade gliomas result from the tumour relentless invasion. miR-29a/b/c downexpressions contribute to several human tumourigenesis. However, their relevance to prognosis and invasion in gliomas remains unclear.Methods:Relationships of miR-29a/b/c and CDC42 expressions to grade and survival-time in 147 human gliomas were analysed by in situ hybridisation and immunohistochemistry. Dual-luciferase reporter assay was used to identify CDC42 as a target of miR-29a/b/c. Underlining mechanisms by which miR-29a/b/c inhibited glioma cell migration and invasion were studied by in vitro and in vivo assays.Results:miR-29a/b/c expressions were inversely correlated with glioma grades, but positively correlated with patients’ survival. Two distinct subgroups of grade I–IV glioma patients with different prognoses were identified according to miR-29a/b/c expressions. miR-29a/b/c overexpressions suppressed glioma cell migration and invasion through targeting CDC42 and subsequently decreasing phosphorylated PAK1/2/3, LIMK1/2 and cofilin, the pivotal downstream effectors of CDC42. Moreover, CDC42 expression was positively correlated with glioma grades, but inversely correlated with miR-29a/b/c expressions and patients’ survival. In glioblastoma cell lines, CDC42-knockdown could mimic the anti-tumour effects of miR-29a/b/c.Conclusions:miR-29a/b/c are important tumour suppressors and novel prognostic biomarkers of gliomas, and miR-29a/b/c and CDC42 are potential therapeutic candidates for malignant gliomas.
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影响因子：
158.5
作者：
Stupp, R;Mason, WP;Ryan, G
通讯作者：
Ryan, G
影响因子：
56.9
作者：
Lagos-Quintana, M;Rauhut, R;Tuschl, T
通讯作者：
Tuschl, T
影响因子：
168.9
作者：
Ricard, Damien;Idbaih, Ahmed;Delattre, Jean-Yves
通讯作者：
Delattre, Jean-Yves
miR-146b-5p通过靶向MMP16抑制胶质瘤迁移和侵袭
影响因子：
9.7
作者：
Li, Yanyan;Wang, Ying;Kong, Yanling
通讯作者：
Kong, Yanling
DOI：
10.1038/nrneurol.2011.100
发表时间：
2011-07-05
期刊：
Nature reviews. Neurology
影响因子：
--
作者：
Riddick G;Fine HA
通讯作者：
Fine HA