OncoTargets and Therapy (Oct 2018)
Regulation of cell proliferation and metastasis by microRNA-593-5p in human gastric cancer
Abstract
Han Yu,1,* Weiyuan Wei,1,2,* Wenlong Cao,1 Zexu Zhan,1 Linhai Yan,2 Kun Wu,1 Dongyi Xie,1 Bin Cai,1 Yubo Xie,3 Qiang Xiao1 1Department of Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China; 2Department of Gastrointestinal Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China; 3Department of Anesthesiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China *These authors contributed equally to this work Background: MicroRNA (miRNA) array analysis has reported that the expression of miR-593-5p is associated with lymph node metastasis in gastric cancer (GC); however, the function and mechanism of miR-593-5p in GC have not been described yet. miR-593-5p has also not been elucidated widely in other cancers. Methods: miR-593-5p expression was detected by quantitative RT-PCR (qRT-PCR) in human GC tissues and cell lines. Cell proliferation was investigated using CCK-8 assays, cell cycle was detected by flow cytometric method, and cell migration and invasion abilities were evaluated by wound-healing and transwell assays. miR-593-5p-influenced gene expression profiles were detected by total gene expression chip method in MGC-803 cells, and miR-593-5p candidate target genes were predicted using bioinformatics methods. The candidate target gene and downstream of miR-593-5p were determined by qRT-PCR, Western blot, and dual-luciferase reporter assays. The effects of miR-593-5p on the growth and metastasis of GC were evaluated by tumor xenograft experiment in vivo. Results: miR-593-5p was frequently downregulated in GC patients and GC cell lines. miR-593-5p was significantly correlated with tumor size and distant metastasis in GC patients. miR-593-5p inhibited cell proliferation, migration, and invasion and also arrested cell cycle at the G0/G1 phase in SGC-7901 and MGC-803 cells in vitro. miR-593-5p also suppressed tumor growth and metastasis in vivo. miR-593-5p influenced gene expression profile in MGC-803 cells. MST4 was indirectly targeted by miR-593-5p. miR-593-5p also downregulated FAK, MMP12, and JUN protein expression. Conclusion: Our study suggests that miR-593-5p may function as a tumor suppressor in GC through a mechanism that regulates JUN pathway via indirectly targeting the MST4 gene. Keywords: miR-593-5p, gastric cancer, MST4, JUN pathway
