Tumor-derived exosomes orchestrate the microRNA-128-3p/ ELF4 / CDX2 axis to facilitate the growth and metastasis of gastric cancer via delivery of LINC01091

It has been manifested that tumor-derived exosomes (Exos) can deliver long noncoding RNAs to participate in gastric cancer (GC) progression. In this research, we intended to dissect out whether tumor-derived Exos carried LINC01091 to afflict the growth and metastasis of GC. GC tissues and human GC cells were attained for RNA and protein quantification. Accordingly, LINC01091, ELF4 , and CDX2 were abundant but microRNA (miR)-128-3p was underexpressed in GC tissues and cells. Exos were isolated from LINC01091-silenced GC cells (Exo-sh-LINC01091). GC cells were co-cultured with Exo-sh-LINC01091 or manipulated with miR mimic, inhibitor, or overexpressing or silencing plasmids. Exo-sh-LINC01091, LINC01091, ELF4 or CDX2 silencing, or miR-128-3p upregulation augmented GC cell proliferative, migrating, and invasive properties. In addition, luciferase, RNA pull-down, and ChIP assays offered evidence supporting the mechanism that LINC01091 bound to miR-128-3p that inversely targeted ELF4 , and ELF4 transcriptionally activated CDX2 by binding to its promoter in GC cells. Moreover, Exo-sh-LINC01091 modulated the miR-128-3p/ ELF4 / CDX2 axis and restrained the tumorigenesis and metastasis in vivo. Conclusively, LINC01091 shuttled by tumor-derived Exos might expedite GC development by activating the ELF4 / CDX2 axis via miR-128-3p downregulation. Graphical abstract