Modulation of microRNA by vitamin D in cancer studies

Vitamin D, a steroid hormone, is well known for its influence in regulating gene expression via the action of the vitamin D receptor, in addition to its classical roles in maintaining calcium homeostasis and bone health. Recently, vitamin D status has been linked to a number of additional nonskeletal diseases, including cancers. Aberrant miRNA profiles have been demonstrated in malignant tissues and in the serum and plasma of cancer patients, leading to investigations into the potential that vitamin D-dependent modulation of miRNA profiles is involved in determining the risk and progression of malignancy. A number of studies, mostly in cell culture models, have demonstrated the modulation of a number of miRNA in a number of cancers; however, results vary depending on the cell line, stimulation concentration, and time of treatment. Additional studies are needed to assess similar relationships in other diseases where risk is linked to vitamin D status. While few studies have been conducted in humans, differences in serum profiles relative to vitamin D levels have been demonstrated. miRNA may provide a link between vitamin D status and disease risk, and this may offer a potential therapeutic avenue. Evidence exists to show that vitamin D can modulate miRNA levels by altering expression of the enzymes involved in miRNA biogenesis and direct and indirect induction of miRNA transcription. However, additional studies are needed to fully elucidate the genetic pathways resulting in modulation of miRNA and to understand the complex interactions between miRNA and vitamin D-related targets.