CircRUNX1 enhances the Warburg effect and immune evasion in non-small cell lung cancer through the miR-145/HK2 pathway

Abstract

Non-small cell lung cancer (NSCLC) is acknowledged as the primary subtype of lung cancer. The Warburg effect, marked by elevated glucose consumption and lactate fermentation, is a prevalent characteristic of NSCLC. The mechanisms by which circRNA mediates the regulation of the Warburg effect and immune evasion in NSCLC remain unclear. This study found an elevated circRNA, circRUNX1, whiche promotes glycolysis and lactate generation, resulting in the infiltration of regulatory T cell (Treg) in NSCLC. circRUNX1 acts as a miR-145 sponge, inhibiting its negative regulation of the target gene HK2, therefore facilitating glycolysis and lactate generation. The accumulation of lactic acid in the tumor microenvironment promotes Treg cell proliferation and aids immune evasion. Functionally, the suppression of circRUNX1 significantly impedes tumor development both in vitro and in vivo. These findings collectively clarity a previously unexamined mechanism linking the circRUNX1/miR-145/HK2 axis in regulation of the Warburg effect and immune evasion in NSCLC.