H19 contributes to aerobic glycolysis, proliferation and immune escape of gastric cancer cells via the miR-519d-3p/LDHA axis

Abstract

Background Long non-coding RNAs (lncRNAs) have been investigated in multiple human cancers including gastric cancer (GC). Our research aims to explore the role of H19 in aerobic glycolysis, proliferation, and immune escape of GC cells.Methods The expression of H19 in GC samples were analyzed using Gene Expression Profiling Interactive Analysis (GEPIA), Gene Expression Omnibus (GEO) data, and real-time quantitative polymerase chain reaction (RT-qPCR) analysis. Glucose consumption and lactate production were applied to assess the aerobic glycolysis of GC cells. Subcellular fractionation, luciferase reporter, and western blot assays certified the binding between genes. CCK-8 and colony formation assays were used to determine GC cell proliferation. Flow cytometry, ELISA, and RT-qPCR assays were applied to analyze the immunosuppressive effect of H19. Results H19 was highly expressed in samples of patients with GC, and associated with tumor growth in vivo. H19 knockdown suppressed glucose consumption, lactate production, proliferation of GC cells by regulating miR-519d-3p/LDHA axis. Both miR-519d-3p depletion and LDHA overexpression could reverse the H19 knockdown-induced decrease in aerobic glycolysis and proliferation. Moreover, conditioned medium (CM) from stable knockdown H19 GC cells modulated the activity of immune cells including γδT cells, Jurkat cells, and tumor-associated macrophages (TAMs) in a lactate dependent manner.Conclusions The H19/miR-519d-3p/LDHA axis mainly contributed to aerobic glycolysis, proliferation, and immune escape of GC cells.