Expression data of A2058-TET2WT, A2058-TET2M, and Mock cells treated under high-g and normal-g

Diabetes is a complex metabolic syndrome characterized by prolonged high blood glucose levels. It is known that diabetes is associated with an elevated risk of cancer, however, the underlying molecular mechanisms are largely unknown. In particular, it remains unclear as to how hyperglycemia may affect epigenetic checkpoints and tumor suppressor pathways, thus enabling oncogenic transformation. Here we show that long-term hyperglycemic conditions adversely impact the anti-tumor epigenetic mark DNA 5-hydroxymethylcytosine (5hmC) through direct regulation of the tumor suppressor and DNA 5mC hydroxymethylase, TET2. We identify TET2 as a novel substrate of the AMP-activated kinase (AMPK).

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Wu D, Hu D, Chen H, Shi G, Fetahu IS, Wu F, Rabidou K, Fang R, Tan L, Xu S, Liu H, Argueta C, Zhang L, Mao F, Yan G, Chen J, Dong Z, Lv R, Xu Y, Wang M, Ye Y, Zhang S, Duquette D, Geng S, Yin C, Lian CG, Murphy GF, Adler GK, Garg R, Lynch L, Yang P, Li Y, Lan F, Fan J, Shi Y, Shi YG