MiR-139-5p inhibits invasion and migration of gastric cancer cells by targeting PAK5 gene to block Wnt/β-catenin signaling pathway
- Author:
- No author available
- Journal Title:
- World Chinese Journal of Digestology
- Issue:
- 4
- DOI:
- 10.11569/wcjd.v29.i4.174
- Key Word:
- miR-139-5p;PAK5基因;Wnt/β-catenin信号通路;胃癌细胞;侵袭;迁移
Abstract： 背景胃癌(Gastric cancer,GC)是人类消化系统最常见的癌症类型,发生局部或全身转移是导致患者预后差的主要原因.微小RNA(microRNA,miRNA)是胃癌发生发展的重要调控因子.然而,miR-139-5p对胃癌细胞侵袭和转移的影响及机制尚不清楚.目的探究miR-139-5p靶向p21活化的激酶5(PAK5)基因调控Wnt/β-catenin信号通路对胃癌细胞侵袭和迁移的影响.方法采用实时荧光定量PCR(qRT-PCR)和Western blot分别检测永生化胃黏膜细胞GES1和不同胃癌细胞SGC-7901、AGS和BGC-823中miR-139-5p和PAK5的表达情况;在胃癌SGC-7901细胞中转染miR-139-5p mimics,qRT-PCR检测转染效果;Transwell侵袭和划痕实验检测过表达miR-139-5p对SGC-7901细胞侵袭和迁移能力的影响;双荧光素酶报告基因实验和Westem blot测miR-139-5p对PAK5的靶向调控关系;Westem blot测过表达miR-139-5p对Wnt/β-catenin信号通路激活的影响.结果胃癌细胞中miR-139-5p的表达水平明显低于正常胃黏膜细胞(P＜0.05),而PAK5 mRNA和蛋白表达水平均明显高于正常胃黏膜细胞(P＜0.05);转染miR-139-5p mimics能够上调SGC-7901细胞中miR-139-5p的表达;过表达miR-139-5p可明显抑制SGC-7901细胞侵袭和迁移能力;双荧光素酶报告基因实验和Western blot检测结果显示,miR-139-5p可靶向负调控PAK5的表达;过表达miR-139-5p后,SGC-7901细胞中Wnt3a、p-连环蛋白(β-catenin)、细胞周期蛋白Dl(CyclinDl)蛋白表达均明显下调.结论miR-139-5p靶向PAK5并通过阻断Wnt/β-catenin信号通路抑制胃癌细胞侵袭和迁移能力.
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