ALKBH5 knockdown suppresses gastric cancer progression by reducing the expression of long non-coding RNA TUG1.

[PURPOSE] This study aimed to explore the relationship between m6A demethylase ALKBH5 and long noncoding RNA TUG1 (TUG1), as well as their effects on proliferation, migration, and angiogenesis in gastric cancer (GC) cells.

[METHODS] The Cancer Genome Atlas (TCGA) database was utilized to analyze the relative expression levels of ALKBH5, TUG1, and vascular endothelial growth factor A (VEGFA). Survival analyses of TUG1, ALKBH5, and VEGFA were performed using the Gene Expression Profiling Interactive Analysis (GEPIA) and Kaplan-Meier databases. The binding sites of TUG1 and ALKBH5 were predicted using the Annolnc2 database. The correlation between ALKBH5 and TUG1 expression was analyzed using the GEPIA database. Subsequently, small interfering RNA (siRNA) targeting ALKBH5 and TUG1 was transfected into SGC-7901 cells, and functional studies were conducted using quantitative real-time polymerase chain reaction (qRT-PCR), CCK-8 assays, colony formation assays, transwell assays, and angiogenesis assays.

[RESULTS] Bioinformatics analysis indicated that ALKBH5, TUG1, and VEGFA were highly expressed in gastric cancer tissues and exhibited a positive correlation. Survival analysis revealed that high expression levels of ALKBH5, TUG1, and VEGFA were significantly associated with poor prognosis in gastric cancer patients. Binding sites for TUG1 and ALKBH5 were identified. Functional experiments demonstrated that the knockdown of ALKBH5 resulted in the downregulation of TUG1, which subsequently reduced the proliferation, invasion, migration, and angiogenesis of gastric cancer cells.

[CONCLUSION] The m6A demethylase ALKBH5 promotes gastric cancer progression by erasing the methylation modification of TUG1 and increasing TUG1 expression. This finding provides a new perspective for the treatment and prognosis assessment of gastric cancer.