ZNF521/EBF1 axis regulates AKR1B1 to promote the proliferation, migration, and invasion of gastric cancer cells.

Although the incidence and death rates of gastric cancer (GC) are decreasing, approximately one million new cases and 800,000 GC-related deaths were reported worldwide in 2018. Currently, the oncogenesis of GC remains unclear, and the demand for novel treatment options are unmet. Here, we explored the role of aldo-keto reductase family 1 member B (AKR1B1) in the progression of GC. The proliferation, migration, and invasion of GC cells were evaluated by CCK-8 assay, wound healing assay, and transwell assay, respectively. The interaction between EBF transcription factor 1 (EBF1) and the promoter region of AKR1B1 was determined by luciferase reporter assay and chromatin immunoprecipitation (ChIP). Gene expression levels were measured by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting assay. The expression of AKR1B1 was elevated in GC cells, resulting in increased cell proliferation, migration, and invasion. Meanwhile, EBF1 was a negative regulator of AKR1B1; its overexpression suppressed AKR1B1 expression and GC progression. Furthermore, knockdown of ZNF521 induced EBF1 expression, thus suppressing AKR1B1 expression and resulting in attenuated GC growth and invasiveness. Notably, knockdown of ZNF521 attenuated GC progression and was rescued by overexpression of AKR1B1. Our current study revealed a novel ZNF521/EBF1/AKR1B1 axis in GC and elaborated its important role in promoting GC progression, providing potential therapeutic targets for anti-GC treatments.