Exosome-transferred LINC01559 promotes the progression of gastric cancer via PI3K/AKT signaling pathway

Increasing evidence indicates that long non-coding RNAs (lncRNAs) are associated with the progression of human cancers. However, the expression level and function of LINC01559 (long intergenic non-protein coding RNA 1559) in gastric cancer (GC) are rarely reported. Here we found that LINC01559 was upregulated in GC tissues based on GEPIA (Gene Expression Profiling Interactive Analysis) and TCGA (The Cancer Genome Atlas) databases. Also, LINC01559 was expressed at a lower level in GC cells than in mesenchymal stem cells (MSCs). In vitro experiments revealed that silencing LINC01559 remarkably hindered GC cell proliferation, migration and stemness. Then, we identified that LINC01559 was transmitted form MSCs to GC cells via the exosomes. Immunofluorescence staining and electron microscope validated the existence of exosomes in GC cells. Mechanistically, LINC01559 sponged miR-1343-3p to upregulate PGK1 (phosphoglycerate kinase 1), therefore activating PI3K/AKT pathway. Moreover, LINC01559 recruited EZH2 (enhancer of zeste 2 polycomb repressive complex 2 subunit) to PTEN (phosphatase and tensin homolog) promoter, inducing the methylation of PTEN promoter and finally resulting in PTEN repression. Of note, LINC01559 targeted both PGK1 and PTEN to promote GC progression by activating PI3K/AKT pathway. Taken together, our study demonstrated that LINC01559 accelerated GC progression via upregulating PGK1 and downregulating PTEN to trigger phosphatidylinositol 3-kinase/AKT serine/threonine kinase (PI3K/AKT) pathway, indicating LINC01559 as a potential biomarker for GC treatment.