MicroRNA-214 promotes the proliferation, migration and invasion of gastric cancer MKN28 cells by suppressing the expression of Dact2

被引:9
作者
Zhao, Lei [1 ]
Fan, Weiwei [2 ]
Fan, Yujing [1 ]
Gao, Shanling [1 ]
机构
[1] Harbin Med Univ, Affiliated Hosp 2, Dept Gastroenterol, 246 Xuefu Rd, Harbin 150086, Heilongjiang, Peoples R China
[2] Heilongjiang Prov Hosp, Dept Infect Internal Med, Harbin 150036, Heilongjiang, Peoples R China
关键词
microRNA-214; Dact2; gastric cancer; CATENIN SIGNALING PATHWAY; EPIGENETIC REGULATION; STEM-CELLS; WNT; METHYLATION;
D O I
10.3892/etm.2018.6771
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
The present study examined the expression of Dapper, antagonist of -catenin 2 (Dact2) and microRNA (miR)-214 in gastric cancer at tissue and cellular levels, and to understand their biological roles. A total of 42 gastric cancer patients were enrolled in the present study. Bioinformatics tool was used to predict the miR molecule that potentially regulates Dact2 expression. To measure the expression of miR-214 and Dact2, reverse transcription-quantitative polymerase chain reaction was employed. Mixed gastric adenocarcinoma type MKN28 cells were transfected with negative control (NC), miR-214 mimics or inhibitor. The CCK-8 assay was used to investigate the proliferation of mixed gastric adenocarcinoma type MKN28 cells. To study migration and invasion abilities of mixed gastric adenocarcinoma type MKN28 cells, the Transwell assay was performed. To determine the expression of Dact2 protein, western blotting was conducted and the rescue assay was utilized to study the biological roles of miR-214 and Dact2 in mixed gastric adenocarcinoma type MKN28 cells. To test whether Dact2 is a direct target of miR-214, the dual luciferase reporter assay was performed. Results indicated that the expression of miR-214 was elevated, but expression of Dact2 mRNA was decreased in gastric cancer tissues, which was closely correlated with the invasion, metastasis, occurrence and development of gastric cancer. Notably, miR-214 promoted the proliferation of mixed gastric adenocarcinoma type MKN28 cells in vitro, whereas but Dact2 inhibited the proliferation of these cells. Downregulation of miR-214 expression or upregulation of Dact2 expression inhibited the migration and invasion of mixed gastric adenocarcinoma type MKN28 cells. Furthermore, miR-214 regulated the expression of Dact2 protein and its downstream -catenin protein in mixed gastric adenocarcinoma type MKN28 cells. Dact2 reversed the effect of miR-214 on the proliferation, migration and invasion of mixed gastric adenocarcinoma type MKN28 cells. In addition, miR-214 directly targeted the 3-UTR seeding region of Dact2 mRNA to regulate its expression. The present study demonstrated that expression of miR-214 was upregulated in gastric cancer tissues, and positively correlated with lymphatic metastasis and clinical staging. In addition, expression of Dact2 was downregulated in gastric cancer tissues and negatively correlated with lymphatic metastasis and clinical staging. Notably, the present findings suggest that miR-214 promoted the proliferation, migration and invasion of mixed gastric adenocarcinoma type MKN28 cells by suppressing the expression of Dact2.
引用
收藏
页码:4909 / 4917
页数:9
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