Hang Cheng, Yan Hui-Shen, Gong Chen, Gao Hua, Mao Qiu-Hui, Zhu Jian-Xin
Department of Gastroenterology, Taicang Affiliated Hospital of Soochow University, The First People's Hospital of Taicang, Suzhou, Jiangsu 215400, P.R. China.
Department of Traditional Chinese Medicine, Medical College of Yangzhou University, Yangzhou, Jiangsu 225001, P.R. China.
Exp Ther Med. 2019 Oct;18(4):2524-2530. doi: 10.3892/etm.2019.7841. Epub 2019 Aug 2.
Gastric cancer (GC) is a global health problem with poor clinical outcomes. The mechanism of its development and progression remains largely unclear. The present study investigated the role of microRNA-9 (miR-9-5p) in the development and progression of GC. Overexpression of miR-9-5p led to reduced expression of neuropilin-1 (NRP-1) in GC cells. Dual-luciferase reporter assay results indicated that miR-9-5p directly targeted NRP-1. Furthermore, overexpression of miR-9-5p in GC cells increased the expression of mesenchymal markers, N-cadherin and vimentin, and decreased the expression of epithelial markers, E-cadherin and β-catenin. Overexpression of miR-9-5p inhibited GC cell proliferation, migration and invasion, and increased the sensitivity of GC cells to the anti-cancer drug cisplatin. By contrast, the opposite effects were observed in GC cells following downregulation of miR-9-5p. Taken together, the present findings suggested that miR-9-5p suppressed NRP-1 expression and inhibited GC cell proliferation and invasion. In addition, miR-9-5p overexpression attenuated GC cell resistance to anti-cancer drugs, which highlighted the potential of miR-9-5p as a target for the treatment of GC.
胃癌(GC)是一个全球性的健康问题,临床预后较差。其发生和发展的机制在很大程度上仍不清楚。本研究探讨了微小RNA-9(miR-9-5p)在胃癌发生和发展中的作用。miR-9-5p的过表达导致胃癌细胞中神经纤毛蛋白-1(NRP-1)的表达降低。双荧光素酶报告基因检测结果表明,miR-9-5p直接靶向NRP-1。此外,miR-9-5p在胃癌细胞中的过表达增加了间充质标志物N-钙黏蛋白和波形蛋白的表达,并降低了上皮标志物E-钙黏蛋白和β-连环蛋白的表达。miR-9-5p的过表达抑制了胃癌细胞的增殖、迁移和侵袭,并增加了胃癌细胞对抗癌药物顺铂的敏感性。相比之下,在miR-9-5p下调后的胃癌细胞中观察到相反的效果。综上所述,本研究结果表明,miR-9-5p抑制NRP-1表达,抑制胃癌细胞增殖和侵袭。此外,miR-9-5p的过表达减弱了胃癌细胞对抗癌药物的耐药性,这突出了miR-9-5p作为胃癌治疗靶点的潜力。