miR-370 regulates cell proliferation and migration by targeting EGFR in gastric cancer.
miR-370 regulates cell proliferation and migration by targeting EGFR in gastric cancer.
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miR-370 通过靶向胃癌中的 EGFR 来调节细胞增殖和迁移。
DOI：
10.3892/or.2017.5660
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发表时间：
2017
期刊：
影响因子：
4.2
通讯作者：
Y. Ba
中科院分区：
文献类型：
--
作者：
T. Ning;Haiyang Zhang;Xinyi Wang;Shuang Li;Le Zhang;T. Deng;Li;Rui Liu;Xia Wang;M. Bai;S. Ge;Hong;Dingzhi Huang;Guoguang Ying;Y. Ba
表皮生长因子受体（EGFR）在约30%的胃癌（GC）病例中过表达，可作为预测抗EGFR治疗临床获益的有效生物标志物。然而，EGFR表达的调节机制仍不清楚。有证据表明，EGFR的表达过程中可能存在转录后调控。本研究旨在探讨miR-370是否参与了这一过程，以及它如何影响GC细胞的生物学行为。在本研究中，我们首先通过EGFR过表达质粒和siRNA确定EGFR在GC中的作用。采用免疫组化和定量RT-PCR（RT-qPCR）方法检测胃癌组织中EGFR蛋白和mRNA的表达水平。应用生物信息学工具和双荧光素酶检测技术对靶向EGFR的相关miRNA进行预测和验证。最后，以人胃癌MGC-803细胞为研究对象，探讨miRNA对胃癌MGC-803细胞增殖和迁移的影响。我们发现，抑制EGFR抑制GC细胞的增殖和迁移。此外，胃癌组织中EGFR蛋白水平比相应配对非癌组织中的EGFR蛋白水平高约4倍，而EGFR mRNA水平仅为相邻非癌组织中的EGFR mRNA水平的约2倍。生物信息学工具预测miRNA-370是EGFR的调节因子，双荧光素酶试验证实miR-370可直接与EGFR mRNA的3 '-非翻译区（3'-UTR）结合。胃癌组织中miR-370与EGFR表达呈负相关。miR-370过表达抑制胃癌细胞的增殖和迁移，而下调miR-370则促进胃癌细胞的增殖和迁移。本研究为阐明胃癌EGFR蛋白表达调控的分子机制提供了新的信息，对指导靶向治疗具有重要的临床意义。
Epidermal growth factor receptor (EGFR) is known to be overexpressed in ~30% of gastric cancer (GC) cases, and may serve as an effective biomarker for predicting the clinical benefit of anti-EGFR therapy. However, the mechanism underlying the regulation of EGFR expression remains unknown. Evidence indicates that post-transcriptional regulation may exist in the process of EGFR expression. In the present study, we aimed to explore whether miR-370 is involved in this process, and how it impacts the biological behaviors of GC cells. In the present study, we first determined the role of EGFR in GC by means of an EGFR overexpression plasmid and siRNAs. Then, the expression levels of EGFR protein and mRNA in GC tissues were analyzed through immunohistochemistry and quantitative RT-PCR (RT-qPCR). Bioinformatics tools and dual-luciferase assay were applied to predict and validate the relevant miRNA targeting EGFR. Finally, human GC MGC-803 cells were selected to explore the effect of miRNA on cell proliferation and migration. We found that suppression of EGFR inhibited the proliferation and migration of GC cells. In addition, the levels of EGFR protein in the GC tissues were ~4 times higher than that in the corresponding paired non-cancerous tissues while the mRNA levels of EGFR were only ~2-fold as high as that in the adjacent non-cancerous tissues. Bioinformatics tools predicted that miRNA-370 was a regulator of EGFR and dual‑luciferase assay validated that miR-370 could directly bind to the 3'-untranslated region (3'-UTR) of EGFR mRNA. Meanwhile, an inverse correlation between miR-370 and EGFR was found in the GC tissues. Overexpression of miR-370 suppressed the proliferation and migration of GC cells, while downregulation of miR-370 promoted proliferation and migration. The present study may provide new information for understanding the molecular mechanism underlying the regulation of EGFR protein expression in GC and may be of important clinical significance to guide targeted therapy.
影响因子：
50.5
作者：
Weiss, G. J.;Bemis, L. T.;Franklin, W. A.
通讯作者：
Franklin, W. A.
影响因子：
2.9
作者：
Friedman JM;Jones PA
通讯作者：
Jones PA
DOI：
10.1073/pnas.0307323101
发表时间：
2004-03-02
影响因子：
11.1
作者：
Calin, GA;Sevignani, C;Croce, CM
通讯作者：
Croce, CM