LINC01224 promotes the Warburg effect in gastric cancer by activating the PI3K/AKT/mTOR/HIF-1α axis

Abstract

BACKGROUND: Gastric cancer (GC) is an aggressive malignancy, and patients with advanced-stage GC have high rates of morbidity. The long intergenic non-protein coding RNA 1224 (LINC01224) functions in the pathogenesis of many cancers. We performed in vitro and in vivo studies of the pathogenesis of GC to investigate the effects and mechanism of LINC01224 in this cancer. METHODS: qRT-PCR was used to measure the expression of LINC01224, and qRT-PCR and western blotting were used to measure the expression of genes in the PI3K/AKT/mTOR/HIF-1α axis (phosphoinositide 3-kinase [PI3K], AKT, mammalian target of rapamycin [mTOR], and hypoxia-inducible factor 1 [HIF-1α]) in GC cells. The function of LINC01224 in GC cells was determined using transfection experiments and measurements of cell viability, cell proliferation, colony formation, apoptosis, cell migration, and cell invasion. Glucose metabolism was evaluated using a glucose uptake assay and measurements of lactate. A tumor xenograft model was used to examine the effect of LINC01224 on GC growth in vivo. RESULTS:Up-regulation of LINC01224 in GC cells activated the PI3K/AKT/mTOR/HIF-1α axis and promoted aerobic glycolysis, thereby increasing cell viability, proliferation, migration, and invasion, and decreasing apoptosis. Down-regulation of LINC01224 had the opposite effects. CONCLUSION: LINC01224 promotes the in vitro and in vivo pathogenesis of GC due to upregulation of aerobic glycolysis by activation of the PI3K/AKT/mTOR/HIF-1α axis. These results imply that future studies of GC should examine the effect of targeting of LINC01224 as a treatment strategy.