When the human genome project mapped its first chromosome in 1999, scientists predicted the human genome would contain over 100,000 active genes. The scientists were shocked to discover that only around 20,000 were eventually identified as active. Non-coding areas make up much of the genome, and they are ultra-conserved — meaning they don’t evolve and are much the same now as they were a million years ago. And, they are much the same in humans as they are in rats. In fact, 95% of your genes are identical to those of a rat.
Around the same time the human genome project started mapping our genes, scientists discovered something called microRNA (miRNA). They are small pieces of RNA found in both plants and animals. It turns out they also regulate gene expression. While these small pieces of RNA don’t code for proteins, they do work on genes but in different ways. They often silence genes, and appear to be designed to silence genes that are out of control, such as in cancer. The human genome may encode over 2000 miRNAs, which may target 30% of all coding genes. More than 700 miRNAs have so far been identified in humans and scientists predict more than another 800 are yet to be discovered.
The first miRNAs were characterized in the early 1990s, but their importance as profound biological regulators was not recognized until the early 2000s. Since then, miRNA research has exploded, revealing multiple roles in both silencing and affecting gene expression. By affecting gene regulation on a grand scale, miRNAs are likely to be involved in most biological processes. Each miRNA may regulate the expression of multiple target genes. Due to their abundant presence and far-reaching potential, miRNAs have all sorts of functions in physiology, from cancer, to the endocrine system, blood formation, fat metabolism, viral infections, nerve growth, insulin secretion, cholesterol metabolism, even directing the shape of a developing limb.
Recently, it has become clear that vitamin D regulates some of these miRNA. Sometimes vitamin D makes more miRNA (upregulates) and sometimes it makes less miRNA (downregulates). Vitamin D regulated miRNA seems also to play a role in silencing and expressing genes through an epigenetic mechanism. Scientists are just beginning to learn how these vitamin D induced changes in miRNA affect our health.
Drs Angeline Giangrecoa and Larisa Nonn of the University of Illinois at Chicago, recently reviewed the research on vitamin D and miRNAs and looked into what kind of relationship there is between the two.
They made the following points:
- MiRNA expression can differentiate breast cancer from benign tissue with high accuracy, as well as particular features associated with breast cancer such as estrogen receptor expression, lymph node metastasis, vascular invasion, and proliferation.
- A tumor suppressive miRNA is induced by activated vitamin D and that miRNA exerts anti-proliferative and anti-migratory effects when expressed in human colon cancer cells.
- One study identified miRNAs in 8 melanoma cells lines that could distinguish melanoma from other solid tumors. In melanoma, some miRNAs are decreased by vitamin D.
- In pregnant women, vitamin D deficiency was associated with differential miRNAs levels compared to women with higher 25(OH)D levels.
- When miRNAs were examined in studies giving 4,000 IU/day of vitamin D, 18 miRNAs were upregulated and 8 were down-regulated.
- All of studies done so far, all but one have identified more miRNAs upregulated by vitamin D than were down-regulated.
- Many of the vitamin D-regulated miRNAs alter cells in a manner consistent with tumor suppressor activity.
The authors concluded,
“Although regulation of any one miRNA by vitamin D3 may not seem significant in cell function, these small changes may add up to the preservation of overall health in persons with vitamin D3 sufficiency. It makes sense that vitamin D3, an essential hormone, modulates many aspects of normal cell function. It is the recent prevalence of vitamin D3 deficiency, and diseases linked to that deficiency, that has brought the identification of mechanisms of vitamin D3 action to forefront of research. In general health practice vitamin D3 is not an intervention or drug, but rather part of overall health and that maintenance of vitamin D3 sufficiency is as important as other markers of health (i.e. low serum cholesterol).”
So how does vitamin D and miRNA play a role in your health? Research is still trying to figure it out, but it’s likely that sufficient vitamin D will correctly regulate your miRNA, whether it upregulates or downregulates specific miRNAs. And it appears that some of vitamin D’s anticancer effects are controlled by miRNA expression.