Fig. 4: DNA methylation mechanisms of H19 regulating autophagy.
From: Long noncoding RNA H19: functions and mechanisms in regulating programmed cell death in cancer
Normally, S-adenosylhomocysteine (SAM) is biosynthesized by methionine and MAT (methionine adenosyl transferase) utilizing ATP for energy supply. Then SAM is converted to SAH (S-adenosylhomocysteine) catalyzed by DNMTs. SAH will be cleaved by S-adenosylhomocysteine hydrolase (SAHH) into homocysteine and adenosine. However, when overexpressed H19 in cancer cells binds with SAHH and inhibits its function, the cleavage of SAH is inhibited, leading to its accumulation [13]. The surplus SAH binds with DNMT3B to prevent its binding with Beclin1, thus allowing its expression. Otherwise, Beclin1 will lose its transcriptional activity by DNMT3B-mediated methylation. The Beclin1 protein then binds with Atg14 or UVRAG to promote autophagy via regulating the formation of autophagic vacuole and maturation and transportation of autophagic vacuole in tumor cells [142, 143].
