A medical study published in the British journal Nature recently showed that hyperglycemia has a negative effect on the level of 5-hydroxymethylcytosine (5hmC), a DNA modification that is affected by cancer. This finding may help explain why diabetes increases the risk of cancer.
Diabetes is a complex metabolic syndrome characterized by persistently high blood glucose levels, often accompanied by serious, life-threatening complications. According to the Global Diabetes Report released by the World Health Organization, global diabetes patients have tripled in the past 40 years, and previous epidemiological studies have shown that diabetes increases the risk of cancer. Hyperglycemia may be the most important cause of diabetes and cancer.
However, researchers are still unclear about the molecular mechanisms behind this correlation, and it is unclear how hyperglycemia induces genetic or epigenetic changes that ultimately lead to cancer.
The researchers found that a tumor suppressor gene, TET2, can catalyze the conversion of 5mC to 5hmC, and this decrease in tumor suppressor gene activity leads to a decrease in the 5hmC level in some cancer patients.
The Harvard Medical School research team found that the level of 5hmC in blood cells in diabetic patients is reduced. In experiments with different cells, the researchers found a "phosphorylated switch" that regulates the stability of TET2 and the level of 5hmC. AMP-activated protein kinase (AMPK) acts as an important nutrient and energy receptor that phosphorylates TET2 and increases its stability. Elevated blood glucose inhibits the activity of AMP-activated protein kinase, resulting in a decrease in the stability of TET2 and a decrease in the level of 5hmC.
Scientists have shown that the hypoglycemic agent metformin can inhibit tumor growth through the AMPK-TET2 pathway, and this result provides new ideas for further clinical research. (Reporter Zhang Mengran)
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