Histone lysine demethylase 3B regulates autophagy via tran-scriptional regulation of GABARAPL1 in leukemia cells

Macroautophagy (hereafter referred to as autophagy), a highly conserved self-digestion process, is critical for maintaining homeostasis in response to various stresses. The autophagy-related protein family, including the GABARAP (GABA type A receptor-associated protein) and LC3 (microtubule-associated protein 1 light chain 3) subfamilies, is crucial for autophagosome bio-genesis. Although the regulation machinery of autophagy in the cytoplasm has been widely stud-ied, its transcriptional and epigenetic regulation mechanisms still require more targeted investi-gations. Here we identify histone lysine demethylase 3B (KDM3B) as a crucial component of au-tophagy on a panel of leukemia cell lines, including K562, THP1, and U937, resulting in tran-scriptional activation of autophagy-related gene GABARAPL1 (GABA type A receptor-associated protein like 1). KDM3B expression promotes autophagosome formation and affects the autophagic flux in leukemia cells under the induction of external stimuli. Notably, RNA-seq and qRT-PCR analysis show that KDM3B knockout inhibited the expression of GABARAPL1. ChIP-qPCR and luciferase assay show that KDM3B associates with GABARAPL1 gene promoter under stimula-tion and enhances its transcription. Our findings demonstrate that KDM3B is critical for regu-lating GABARAPL1 gene and influencing the process of autophagy in leukemia cells. These results provide new insight for exploring the relationship between autophagy and KDM3B epigenetic regulation in leukemia.