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

Abstract

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.

Deciphering the genomic and lncRNA landscapes of aerobic glycolysis identifies potential therapeutic targets in pancreatic cancer

“…Moreover, FEZF1-AS1 has been demonstrated to promote the glycolytic phenotypes of colorectal cancer by regulating PKM2 signaling 18 . From the therapeutic point of view, we therefore verified the roles of LINC01559 and UNC5B-AS1, which have been implicated in several oncogenic processes but not involved in glycolysis 19 - 23 . Data from the TCGA + GTEx portal showed that LINC01559 and UNC5B-AS1 were highly expressed in the tumor tissues (n = 179) compared with normal pancreas samples (n = 171) ( Fig.…”

A Novel Autophagy-Related IncRNAs Signature for Prognostic Prediction and Clinical Value in Patients With Pancreatic Cancer

“…Among the six selected ARlncRNAs, LINC01559 was reported to be upregulated in renal cell carcinoma, gastric cancer, PC, and hepatocellular carcinoma (Chen B. et al, 2018;Chen et al, 2020;Dong et al, 2020;Lou et al, 2020;Wang et al, 2020). Moreover, we found that the expression of LINC01559 was significantly increased in both serum and tumor tissues of PC patients, indicating that LINC01559 could serve as a diagnostic biomarker.…”

ZEB1-induced LINC01559 expedites cell proliferation, migration and EMT process in gastric cancer through recruiting IGF2BP2 to stabilize ZEB1 expression

“…For example, HOTAIR can induce gene silencing through its interplay with PRC2 39 . Importantly, a recent study has also verified that LINC01559 can recruit E2H2 to PTEN promoter to activate PI3K/AKT pathway in GC cells 40 . This finding complements the shortcomings of our present work to some extent.…”