miR-370 regulates cell proliferation and migration by targeting EGFR in gastric cancer

被引:29
|
作者
Ning, Tao
Zhang, Haiyang
Wang, Xinyi
Li, Shuang
Zhang, Le
Deng, Ting
Zhou, Likun
Liu, Rui
Wang, Xia
Bai, Ming
Ge, Shaohua
Li, Hongli
Huang, Dingzhi
Ying, Guoguang
Ba, Yi [1 ,2 ]
机构
[1] Tianjin Med Univ, Canc Inst & Hosp, Natl Clin Res Ctr Canc, Key Lab Canc Prevent & Therapy, Tianjin 300060, Peoples R China
[2] Tianjins Cinical Res Ctr Canc, Tianjin 300060, Peoples R China
基金
中国国家自然科学基金;
关键词
miR-370; gastric cancer; EGFR; cell proliferation; migration; LUNG-CANCER; TUMOR SUPPRESSORS; UP-REGULATION; MICRORNA; EXPRESSION; SURVIVAL; THERAPY; PROGRESSION; NETWORK; GENES;
D O I
10.3892/or.2017.5660
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Epidermal growth factor receptor (EGFR) is known to be overexpressed in similar to 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 similar to 4 times higher than that in the corresponding paired non-cancerous tissues while the mRNA levels of EGFR were only similar to 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.
引用
收藏
页码:384 / 392
页数:9
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