miR-5590-3p inhibited tumor growth in gastric cancer by targeting DDX5/AKT/m-TOR pathway.
Recent evidence suggests that microRNAs play important roles in the negative post-transcriptional regulators with altered expression levels found in gastric cancer (GC). Therefore, we employed explore the anti-cancer miRNA and the potential mechanisms by which miRNAs modulate GC progression. We have predicted GC miRNA expression data sets in TargetScan. miR-5590-3p is higher in adjacent nonmalignant tissue than in cancer tissue in 42 pairs of GC tissues. Functional assays, CCK-8 and colony formation assay, were used to determine the Anti-cancer role of miR-5590-3p in human GC progression. In addition, Ago2-based RIP and dual-luciferase reporter assay were conducted to study the miR-5590-3p as a direct target of DDX5. Next, Xenograft nude mouse models were used to determine the role of miR-5590-3p in GC tumorigenicity in vivo. Upregulation of miR-5590-3p suppressed GC cell proliferation, whereas downregulation of miR-5590-3p promoted GC proliferation in vitro. Furthermore, we identified DDX5 as a direct target of miR-5590-3p, and that the biological function of miR-5590-3p during GC progression in vitro and in vivo is through the DDX5/AKT/m-TOR pathway and downstream cyclinD1 and CDK2 expression. Finally, we confirmed the effect of miR-5590-3p directly targeting DDX5 on the development of gastric cancer through salvage experiments in vivo and in vitro.
['Wu|Nan|N|', 'Han|Yuying|Y|', 'Liu|Haiming|H|', 'Jiang|Mingzuo|M|', 'Chu|Yi|Y|', 'Cao|Jiayi|J|', 'Lin|Junchao|J|', 'Liu|Yuanning|Y|', 'Xu|Bing|B|', 'Xie|Xin|X|']
D000818:Animals D045744:Cell Line, Tumor D049109:Cell Proliferation D053487:DEAD-box RNA Helicases D006801:Humans D051379:Mice D008807:Mice, Inbred BALB C D008819:Mice, Nude D035683:MicroRNAs D009374:Neoplasms, Experimental D051057:Proto-Oncogene Proteins c-akt D013274:Stomach Neoplasms D058570:TOR Serine-Threonine Kinases
AKT Gastric cancer (GC) DEAD (Asp-Glu-Ala-Asp) box helicase 5 (DDX5) mTOR microRNA-5590-3p (miR-5590-3p)