RESUMO
Type 2 diabetes mellitus (T2DM) is a frequent comorbidity of cancer. Hyperinsulinemia secondary to T2DM promotes cancer progression, whereas antidiabetic agents, such as metformin, have anticancer effects. However, the detailed mechanism for insulin and metformin-regulated cancer cell proliferation remains unclear. This study identified a mechanism by which insulin upregulated the expression of c-Myc, sterol regulatory element-binding protein 1 (SREBP1), and acetyl-coenzyme A (CoA) carboxylase 1 (ACC1), which are important regulators of lipogenesis and cell proliferation. Thymine DNA glycosylase (TDG), a DNA demethylase, was transactivated by c-Myc upon insulin treatment, thereby decreasing 5-carboxylcytosine (5caC) abundance in the SREBP1 promoter. On the other hand, metformin-activated AMP-activated protein kinase (AMPK) increased DNA methyltransferase 3A (DNMT3A) activity to increase 5-methylcytosine (5mC) abundance in the TDG promoter. This resulted in decreased TDG expression and enhanced 5caC abundance in the SREBP1 promoter. These findings demonstrate that c-Myc activates, whereas AMPK inhibits, TDG-mediated DNA demethylation of the SREBP1 promoter in insulin-promoted and metformin-suppressed cancer progression, respectively. This study indicates that TDG is an epigenetic-based therapeutic target for cancers associated with T2DM.
RESUMO
The study of cnidarian-dinoflagellate endosymbiosis in octocorals is becoming increasingly important. As symbiotic gastrodermal cells (SGCs) are the key cells in a symbiotic relationship, obtaining SGCs and studying their functions represent an urgent need. The majority of the cells dissociated from octocoral tissues consist of host cells and algal cells, and very few intact SGCs can be observed. To solve this problem, we developed a new method to collect large amounts of SGCs from octocorals. We incubated the tissue of Sinularia flexibilis in high-salinity (60‱) filtered seawater for 6 h and were able to collect more than 18 times the number of SGCs from the control group. To test the quality of the dissociated cells, we performed three assays to evaluate their cell viability. All three assays demonstrated that cell viability was good after incubating in a high-salinity solution. We also used two other octocorals, Paralemnalia thyrsoides and Sinularia compressa, to perform the same experiment, and the results were similar to those for Sinularia flexibilis. Therefore, a high-salinity-induced increase in the SGC ratio is a common phenomenon among octocorals. This method allows researchers to collect large amounts of SGCs from octocorals and helps us to better understand the complex molecular interactions in cnidarian-dinoflagellate endosymbiosis.
