MicroRNA-331-3p inhibits epithelial-mesenchymal transition by targeting ErbB2 and VAV2 through the Rac1/PAK1/β-catenin axis in non-small-cell lung cancer
MicroRNA-331-3p inhibits epithelial-mesenchymal transition by targeting ErbB2 and VAV2 through the Rac1/PAK1/β-catenin axis in non-small-cell lung cancer
复制标题
MicroRNA-331-3p 通过 Rac1/PAK1/β-catenin 轴靶向 ErbB2 和 VAV2，抑制非小细胞肺癌中的上皮间质转化
DOI：
10.1111/cas.14014
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发表时间：
2019-06-01
期刊：
影响因子：
5.7
通讯作者：
Zhang, Chunfang
中科院分区：
文献类型：
--
作者：
Li, Xizhe;Zhu, Jiali;Zhang, Chunfang
已经报道microRNA在非小细胞癌（NSCLC）的发展中起关键作用，但microRNA（miR）-331-3p在NSCLC中的作用仍不清楚。本研究采用定量RT-PCR方法检测miR-331 - 3p在NSCLC肿瘤组织及癌旁正常组织中的表达水平，分析miR-331 - 3p表达与患者临床病理特征的关系。在体外和体内测定miR-331 - 3p对NSCLC细胞的上皮-间质转化（EMT）、迁移和转移的影响。通过荧光素酶报告基因分析、蛋白质印迹分析、免疫组织化学染色和拯救分析鉴定miR-331 - 3p的直接功能靶标。通过免疫荧光、免疫沉淀和Rac1活性检测鉴定miR-331 - 3p调控的下游通路。我们的研究结果表明，miR-331 - 3p在NSCLC肿瘤组织中显著下调，且与临床病理特征相关，miR-331 - 3p可作为NSCLC患者独立的预后标志物。此外，miR-331 - 3p在体外和体内显著抑制NSCLC细胞的EMT、迁移和转移。ErbB2和VAV 2都是miR-331 - 3p的直接功能靶点。miR-331 - 3 p通过ErbB 2和VAV 2靶向调节Rac 1、PAK 1和β-连环蛋白的活性。这些结果表明，miR-331 - 3p通过Rac1/PAK1/β-catenin轴靶向ErbB2和VAV 2抑制NSCLC中的EMT、迁移能力和转移能力。
MicroRNAs have been reported to play critical roles in the regulation of non-small-cell cancer (NSCLC) development, but the role of microRNA (miR)-331-3p in NSCLC is still unclear. In this study, the expression levels of miR-331-3p in NSCLC tumor tissues and adjacent normal tissues were examined by quantitative RT-PCR, and the relationship between miR-331-3p expression and patient clinicopathological characteristics was analyzed. The effects of miR-331-3p on epithelial-mesenchymal transition (EMT), migration, and metastasis of NSCLC cells were determined in vitro and vivo. Direct functional targets of miR-331-3p were identified by luciferase reporter assay, western blot assay, immunohistochemical staining, and rescue assay. The downstream pathway regulated by miR-331-3p was identified by immunofluorescence, immunoprecipitation, and Rac1 activity examination. Our results showed that miR-331-3p was significantly downregulated in NSCLC tumor tissues and was correlated with clinicopathological characteristics, and miR-331-3p could be an independent prognostic marker for NSCLC patients. Furthermore, miR-331-3p significantly suppressed EMT, migration and metastasis of NSCLC cells in vitro and in vivo. Both ErbB2 and VAV2 were direct functional targets of miR-331-3p. The activities of Rac1, PAK1, and beta-catenin were regulated by miR-331-3p through ErbB2 and VAV2 targeting. These results indicated that miR-331-3p suppresses EMT, migratory capacity, and metastatic ability by targeting ErbB2 and VAV2 through the Rac1/PAK1/beta-catenin axis in NSCLC.