Regulator of G-protein signaling 3 targeted by miR-126 correlates with poor prognosis in gastric cancer patients
Regulator of G-protein signaling 3 targeted by miR-126 correlates with poor prognosis in gastric cancer patients
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miR-126 靶向的 G 蛋白信号传导 3 调节因子与胃癌患者的不良预后相关
DOI：
10.1097/cad.0000000000000446
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发表时间：
2017-02-01
影响因子：
2.3
通讯作者：
Zhu, Zhenggang
中科院分区：
文献类型：
--
作者：
Wang, Junqing;Zhou, Yunyun;Zhu, Zhenggang
Wnt/ β -连环蛋白信号通路主导着包括细胞增殖、分化和上皮-间质转化在内的许多细胞过程，在人类恶性肿瘤中起着至关重要的作用。g蛋白信号3 （regulatory of G-protein signaling 3, RGS3）是参与Wnt/ β -catenin信号通路的关键分子，作为肿瘤治疗的潜在靶点值得深入研究。在本研究中，我们通过分析NCBI公共数据库中两个独立的胃癌mRNA微阵列数据集，发现RGS3在胃癌（GC）肿瘤样本中与正常样本相比显著上调。基于我们自己的102个配对GC标本和3个GC细胞系的结果，进一步的免疫组织化学分析和western-blot实验证实了这一发现。我们发现RGS3的高表达与TNM晚期和更具侵略性的恶性行为有关。此外，RGS3过表达与较差的总生存期和无进展生存期结果的关联表明，RGS3具有作为GC分子治疗靶点的潜力。有趣的是，我们的通路分析和后续的双荧光素酶报告试验显示，RGS3 mRNA和GC抑制剂microRNA-126之间存在直接的3'-非翻译区结合位点。综上所述，我们的研究结果表明，microRNA-126通过转录后调控调控的RGS3过表达与GC患者预后不良有显著相关性。版权所有2017威科集团有限公司版权所有。
The Wnt/beta-catenin signaling pathway dominates numerous cellular processes including cell proliferation, differentiation, and epithelial-mesenchymal transition, which play a crucial role in human cancer malignancies. Regulator of G-protein signaling 3 (RGS3) is a pivotal molecule involved in the Wnt/beta-catenin signaling pathway, which is worthy of intensive research as a potential target in cancer treatment. In this study, we found that RGS3 is significantly upregulated in gastric cancer (GC) tumor samples compared with normal samples from the analysis of two independent GC mRNA microarray datasets in the NCBI public database. Further immunohistochemistry assay and western-blot experiments confirmed this finding on the basis of the results of our own 102 paired GC specimens and three GC cell lines. We found that a high expression of RGS3 is associated with advanced TNM stages and more aggressive malignant behaviors. In addition, the association of overexpression of RGS3 and poor overall survival and progression-free survival outcomes suggests that RGS3 has the potential to serve as a molecular therapy target for GC. Interestingly, our pathways analysis and the follow-up dual-luciferase reporter assay showed that there is a direct 3'-untranslated region binding site between RGS3 mRNA and microRNA-126, a GC inhibitor. On the basis of all the above evidences, our findings suggest that overexpressed RGS3 regulated by microRNA-126 through the post-transcriptional modulation is associated significantly with a poor prognosis of GC patients. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.