Inhibition of cell proliferation and induction of autophagy by KDM2B/FBXL10 knockdown in gastric cancer cells

Gastric cancer is difficult to cure due to its clinical heterogeneity and the complexity of its molecular mechanisms. KDM2B, a member of the JHDM family, functions as a histone lysine demethylase. However, the role and mechanisms of KDM2B in gastric cancer have not been elucidated. Here, we showed that KDM2B is commonly expressed in gastric cancer cells. The downregulation of KDM2B immediately induces autophagy, followed by the inhibition of proliferation. The compound 3-methyladenine (3-MA), an inhibitor of autophagy, largely rescues autophagy and the inhibition of cell proliferation induced by KDM2B knockdown. In this process, we observed a downregulation of the phosphorylation of Akt and its downstream effectors mTOR and p70S6K and an upregulation of Erk phosphorylation after KDM2B knockdown. In a xenograft model, the downregulation of KDM2B can inhibit tumour growth. The conversion of LC3-I to LC3-II also decreased concomitantly in vivo, which is a hallmark of autophagy. Taken together, our study was the first to demonstrate a novel regulatory role of KDM2B in autophagy and cell growth in gastric cancer cells. Our findings suggest that KDM2B may serve as a novel therapeutic target for gastric cancer therapy.