PRDX2 promotes gastric cancer progression by forming a feedback loop with PKM2/STAT3 axis

Abstract

Peroxiredoxin 2 (PRDX2) is an antioxidant enzyme that has been reported to be overexpressed in various cancers. However, the role of PRDX2 in gastric cancer progression and its underlying mechanism remains unclear. Herein, we revealed the function of PRDX2 in gastric cancer progression and explored its molecule mechanism. We identified that PRDX2 was upregulated and associated with poor prognosis in gastric cancer. The knockdown of PRDX2 inhibited the proliferation, migration and invasion of gastric cancer cells in vitro and suppressed tumor growth in vivo. Mechanistically, PRDX2 interacted with PKM2 (pyruvate kinase isozyme type M2) and protected PKM2 from ubiquitination and degradation, which enhanced glycolysis in gastric cancer cells. The interaction between PRDX2 and PKM2 also enhanced the binding affinity between PKM2 and importin α5, which induced PKM2 nuclear translocation and activated STAT3 signaling pathway. In addition, STAT3 (signal transducer and activator of transcription 3) was identified to bind to PRDX2 gene promoter and upregulate PRDX2 expression, which forms a positive regulatory feedback loop in gastric cancer cells. The present study unravels the biological role of PRDX2 in cancer progression and illustrates the underlying molecular mechanism, which may provide a potential therapeutic target for gastric cancer.