miRNA and diseaseFebruary 21, 2012

miRNAs are post-transcriptional regulators of gene expression that bind to complementary sequences on target messenger RNA transcripts (mRNAs) present inside the cell, usually resulting in translational repression or target degradation and gene silencing.

Transgenic mice that over-express or lack specific miRNAs have provided insight into the role of small RNAs in various malignancies. Several miRNAs have been found to have links with some types of cancer. MicroRNA-21 is one of the first microRNAs that was identified as an onco-miR. A study of genetically modified mice altered to produce oncogene c-Myc implicated in several cancers — shows that miRNA has an effect on the development of cancer. Mice that were engineered to produce an excess of miRNAs found in lymphoma cells developed the disease within 50 days and died two weeks later. In contrast, mice without the surplus miRNA lived over 100 days. Leukemia can be caused by the insertion of a viral genome next to the 17-92 array of microRNAs leading to increased expression of this microRNA.

A mutation of miR-96 causes hereditary progressive hearing loss. A mutation in the seed region of miR-184 causes hereditary keratoconus with anterior polar cataract. Deletion of the miR-17~92 cluster causes skeletal and growth defects.

Another study found that two types of miRNA inhibit expression of the E2F1 protein, which regulates cell proliferation. miRNA appears to bind to messenger RNA before it can be translated to proteins that switch genes on and off.

miRNA “signatures” may enable classification of cancer. By measuring expression levels of some 217 genes encoding miRNA, scientists were able to distinguish several types of cancer. This will allow doctors to determine the original tissue type which spawned a cancer and to be able to target a treatment course based on the original tissue type. miRNA profiling has already been able to determine whether patients with chronic lymphocytic leukemia had slow growing or aggressive forms of the cancer.

A novel miRNA-based screening assay for the detection of early-stage colorectal cancer has been developed and is currently in clinical trials. Early results showed that blood plasma samples collected from patients with early, resectable (Stage II) colorectal cancer could be distinguished from those of sex-and age-matched healthy volunteers. Sufficient selectivity and specificity could be achieved using small (less than 1 mL) samples of blood. The test has potential to be a cost-effective, non-invasive way to identify at-risk patients who should undergo colonoscopy.

Another role for miRNA in cancers is to use their expression level as a prognostic, for example one study on NSCLC samples found that low miR-324a levels could serve as a prognostic indicator of poor survival, another found that either high miR-185 or low miR-133b levels correlated with metastasis and poor survival in colorectal cancer.

The global role of miRNA function in the heart has been addressed by conditionally inhibiting miRNA maturation in the murine heart, and has revealed that miRNAs play an essential role during its development. miRNA expression profiling studies demonstrate that expression levels of specific miRNAs change in diseased human hearts, pointing to their involvement in cardiomyopathies. Furthermore, studies on specific miRNAs in animal models have identified distinct roles for miRNAs both during heart development and under pathological conditions, including the regulation of key factors important for cardiogenesis, the hypertrophic growth response, and cardiac conductance.

Extra-cellular RNAs were first identified in the blood just three years ago. In September, a Chinese research team reported that fragments of genetic material known as microRNAs (miRNA) are making their way from vegetables into the human bloodstream. Even more surprising, these bits of plant genome may affect health suggesting that some biomolecules can remain active even after digestion.

Biochemist Chen-Yu Zhang of Nanjing University suspected that foreign miRNA might also be present there. “I had the crazy idea to check for nonhuman molecules,” Zhang says. He and his team tested hundreds of volunteers and found about 50 different kinds of plant miRNAs in their blood samples. The scientists noticed that one such molecule, called MIR168a—which is abundant in rice and plays a role in plant development—paired up with a piece of human RNA that helps remove “bad” LDL cholesterol from the bloodstream. Follow-up tests in human cell cultures confirmed that MIR168a interferes with production of a cholesterol-clearing protein. And an experiment with mice showed that LDL cholesterol stuck around longer in the blood of the animals who had eaten rice than in those who had not.

Human stem cells derived from menstrual bloodDecember 19, 2011

Stem cells can be obtained from women’s menstrual blood derived from the endometrium. The cells display stem cell markers such as Oct-4, SSEA-4, Nanog, and c-kit (CD117), and have the potent ability to differentiate into various cell types, including the heart, nerve, bone, cartilage, and fat. There has been no evidence of teratoma, ectopic formation, or any immune response after transplantation into an animal model. These cells quickly regenerate after menstruation and secrete many growth factors to display recurrent angiogenesis. The plasticity and safety of the acquired cells have been demonstrated in many studies. Menstrual blood-derived stem cells (MenSCs) provide an alternative source of adult stem cells for research and application in regenerative medicine. The article was recently published in J Zhejiang Univ Sci B. 2011 May;12(5):372-80 (http://www.ncbi.nlm.nih.gov/pubmed/21528491)

Artificial blood for the armyDecember 8, 2011

The Pentagon recently announced the introduction of artificial blood for the military forces of the U.S. Army. Timely transfusion of blood is often lifesaving in the military. This development is also of a great importance to global health. Given the importance, complexity and high cost of research and development, the first who could address the problem was the military. The artificial blood is being developed in a biotechnological company in Ohio, which has already received the approval of the first prototypes. According to official sources at the Pentagon, properties of the artificial blood cells and plasma will be virtually indistinguishable from those of normal blood.

There are several major problems associated with use of donated blood, – it is perishable, it has to be of a proper blood type and it has to be stored in place where it may be needed or delivered to often remote and not easily accessible places. In the case of an artificial blood, all these problems can be easily solved. The Pentagon has estimated that artificial blood would cost 4 times less than donated blood.