Fig. 4

Regulation on the expression and/or function of ALKBH5 in cancers. a Epigenetic modulators of ALKBH5. Histone modifications involved in ALKBH5 transcriptional activation and their modulators (left); LKB1 loss upregulates ALKBH5 by inducing 5mC DNA hypermethylation of the CTCF motif on ALKBH5’s promoter, preventing CTCF binding and enhancing active histone modifications (middle); Histone modifications involved in ALKBH5 transcriptional inactivation and their modulators (right). HBx HBV X protein, MLL Myeloid/lymphoid or mixed-lineage leukemia protein, WDR5 WD-40 Repeat Protein 5, EP300 E1A-associated protein p300, LKB1 Serine/threonine-protein kinase STK11, CTCF CCCTC-binding factor, KDM4C Lysine-specific demethylase 4C, JMJD2B/1C Jumonji domain-containing protein 2B/1C. b Transcription factors of ALKBH5. Transcription activators and repressors bind to promoter or enhancer of ALKBH5 DNA to control ALKBH5 transcription; Hypoxia-inducible factors (HIFs) activate ALKBH5 transcription in response to local hypoxia in cancer. MYB Proto-oncogene c-Myb, RUNX2 Runt-related transcription factor 2, PBX3 Pre-B-cell leukemia transcription factor 3, p53 Cellular tumor antigen p53, HIF-1/2α Hypoxia-inducible factor 1/2-alpha. c Non-coding RNA partners of ALKBH5. Long non-coding RNAs (lncRNAs) function as scaffolds to enhance ALKBH5 binding to their antisense mRNAs; microRNA (miRNA) miR-193a-3 interacts with 3′UTR of ALKBH5 mRNA and promotes its degradation, while ALKBH5 demethylates and suppresses miR-193a-3p maturation in turn; Circular RNA (circRNA) cIARS interacts with ALKBH5 and represses its regulatory effect on BCL2 mRNA. d Other regulators of ALKBH5. ALKBH5 is positively regulated by TLR4 in ovarian cancer cells after co-culture with M2 macrophages; DDX3 interacts with ALKBH5 and enhances demethylation activity of ALKBH5. TLR4 Toll-like receptor 4, DDX3 DEAD box protein 3, X-chromosomal