Investigation Of The Effect And Mechanism Of Targeting KDM1A To Suppress Lung Cancer Cell Growth

With the continuous improvement of human living standards,cancer has become a major killer of human life and health.According to statistics,among many common malignant tumors,the mortality rate of lung cancer is as high as the first among many common malignant tumors.ORY-1001,an inhibitor of covalent lysine(K)-specific demethylase 1A(KDM1A),has been used as a therapy for the treatment of acute leukemia.However,the underlying mechanisms of anticancer are still not fully elucidated.Here,we report that KDM1 A is highly expressed in lung cancers,where it appears to drive aggressive growth.Furthermore,lung cancer patients with higher KDM1 A levels have worse survival outcomes than patients with lower KDM1 A levels.Interestingly,ORY-1001 significantly inhibited the cell proliferation,colony formation,cell cycle,and induced apotosis,by regulating the Warburg effect through controlling Hexokinases 2(HK2)expression.As we know,in order to adapt to the harsh living environment,the tumor cells are more likely to consume glucose through the glycolysis pathway to obtain the energy of their own growth and proliferation.Therefore,we explored the big sign of energy metabolism of tumor cells and found that the expression of the key metabolic enzyme hexokinase II(HK2)in the glycolytic pathway has changed,further affecting the "Warburg effect".and the lung cancer proliferation can be restored after supplementing HK2.In summary,these results indicate that ORY-1001 could inhibit the growth of lung cancer cells via regulating the Warburg effect by controlling HK2.