Understanding the Role of Selenium in Reactive Oxygen Species Management in Colorectal Cancers

Epidemiological and experimental studies have linked low levels of dietary selenium to cancer onset and progression, but the role of selenium in disease etiology is complicated and still under investigation. Selenium is found in selenocysteine, a key component of the glutathione peroxidase and thioredoxin reductases based selenoproteins that detoxify reactive oxygen species (ROS) and maintain redox homeostasis. Selenoprotein synthesis requires many factors and includes specific tRNA modifications catalyzed by Alkylation repair homolog 8 (ALKBH8). The human TRM9-like (hTRM9L) protein is functionally homologous to the methyltransferase domain of ALKBH8, and we have previously published that hTRM9L gene expression is turned off in late stage colorectal cancer. Further re-expression of hTRM9L in late stage colorectal cancer cells turns off tumor growth. The cellular function of the tumor growth suppressor hTRM9L is unknown, but our current model has hTRM9L regulating the activity of ALKBH8 to affect selenoprotein synthesis, selenium utilization, and ROS detoxification. We have determined that in colorectal cancer cells, (SW480-hTRM9L+ and SW620 cells reengineered to express hTRM9L) the expression of the hTRM9L gene correlates with a selenium induced proliferative effect (10 μM, p