Regulation of cell proliferation and metastasis by microRNA-593-5p in human gastric cancer.
Regulation of cell proliferation and metastasis by microRNA-593-5p in human gastric cancer.
复制标题
microRNA-593-5p对人胃癌细胞增殖和转移的调控
DOI：
10.2147/ott.s178151
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发表时间：
2018
影响因子：
4
通讯作者：
Xiao Q
中科院分区：
文献类型：
--
作者：
Yu H;Wei W;Cao W;Zhan Z;Yan L;Wu K;Xie D;Cai B;Xie Y;Xiao Q
MicroRNA（miRNA）阵列分析报道miR-593-5p的表达与胃癌（GC）的淋巴结转移相关；然而，miR-593-5p在GC中的功能和机制尚未被描述。 miR-593-5p 在其他癌症中也尚未得到广泛阐明。通过定量 RT-PCR (qRT-PCR) 检测人 GC 组织和细胞系中的 miR-593-5p 表达。采用CCK-8法检测细胞增殖，采用流式细胞术检测细胞周期，采用伤口愈合和Transwell实验评价细胞迁移和侵袭能力。采用全基因表达芯片法检测MGC-803细胞中miR-593-5p影响的基因表达谱，并利用生物信息学方法预测miR-593-5p候选靶基因。通过 qRT-PCR、Western blot 和双荧光素酶报告基因测定确定候选靶基因和 miR-593-5p 下游。通过体内肿瘤异种移植实验评估miR-593-5p对GC生长和转移的影响。 miR-593-5p 在 GC 患者和 GC 细胞系中经常下调。 miR-593-5p与GC患者的肿瘤大小和远处转移显着相关。 miR-593-5p 在体外抑制 SGC-7901 和 MGC-803 细胞的细胞增殖、迁移和侵袭，并将细胞周期阻滞在 G0/G1 期。 miR-593-5p 还在体内抑制肿瘤生长和转移。 miR-593-5p 影响 MGC-803 细胞中的基因表达谱。 MST4 是 miR-593-5p 间接靶向的。 miR-593-5p 还下调 FAK、MMP12 和 JUN 蛋白表达。我们的研究表明，miR-593-5p 可能通过间接靶向 MST4 基因来调节 JUN 通路的机制在 GC 中发挥肿瘤抑制因子的作用。
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. 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. 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. 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.