OncoTargets and Therapy (May 2019)
MiR-1284 suppresses gastric cancer progression by targeting EIF4A1
Abstract
Weiyuan Wei,1,* Wenlong Cao,1,* Zexu Zhan,1 Linhai Yan,2 Yubo Xie,3 Qiang Xiao11Department of Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 2Department of Gastrointestinal Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 3Department of Anesthesiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China *These authors contributed equally to this workBackground: MicroRNAs (miRNAs) play a key role in the development of gastric cancer (GC). MiRNA arrays showed that lymph node metastasis in GC is correlated with the expression of miR-1284. Although its function and mechanisms in GC have not been fully described, the regulation of EIF4A1 by miR-1284 and its role in drug-resistant GC has been reported in our previous studies.Methods: qRT-PCR was used to study the level of miR-1284 expression in GC cell lines and tissues. Subsequently, the CCK-8 assay was used to detect cell proliferation, while transwell assay was used to detect invasion and migration of the GC cells. Flow cytometry was used to detect the effect of miR-1284 on GC cells in vivo by building subcutaneous GC nude mice transplantation tumor model. In addition, the influence of miR-1284 gene expression profile in SGC-7901 cells was detected by total gene expression chip, and the target gene of miR-1284 was detected by luciferase reporter assay, qRT-PCR, and western blotting.Results: The miR-1284 level was down-regulated in GC tssues and cell lines. MiR-1284 was significantly associated with tumor size, degree of differentiation and patients’ distant metastasis. MiR-1284 inhibited invasion, migration, and proliferation of GC cells. During the G1/S phase, miR-1284 arrested the cycle of GC cells in vitro. MiR-1284 also suppressed tumor from growing and metastasizing in xenograft models as well as influenced the gene expression profile in SGC-7901 cells. Also, EIF4A1 was the direct target gene for miR-1284. Further, an inverse correlation between the miR-1284 expression and EIF4A1 was found in GC tissues. Over-expressed miR-1284 decreased c-Myc, MMP12, JUN expression, while increased CDH1 expression.Conclusion: These data suggested that miR-1284 acts as a tumor suppressor, and directly blocked EIF4A1 in GC.Keywords: MiR-1284, gastric cancer, EIF4A1, metastasis, proliferation
