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New research reveals the role played by microRNA in the development of colorectal cancer and shows it could be a key target for treatments.

A study into the role played by the molecule in bowel cancer was carried out by an international team which included scientists based at The Institute of Cancer Research, London, the University of Glasgow and Ohio State University in the US.

Their findings are published in the journal Cancer Cell, with funding for the UK research team coming from the Kimmel Cancer Foundation, Cancer Research UK, The Marie Curie Actions Programme and a Scottish Senior Clinical Research Fellowship.

Scientists discovered that MicroRNA 135b is employed by a number of cancer genes to drive the development of the disease.

They believe drugs targeted at the molecule could eliminate the effects of multiple cancer-causing mutations, while tests for it could identify those with the most aggressive form of the disorder.

An analysis of 485 people with bowel cancer found that levels of microRNA 135b were at least four times as high in tumours as in healthy tissue. Patients with the highest amount of the microRNA survived for the least amount of time.

A study conducted on mouse models found that blocking the micro-RNA stopped tumour growth. In half of the animals, tumours regressed so dramatically that they could no longer be seen by imaging, while the animals displayed no side-effects.

Additionally, a number of known cancer gene variations, such as APC, PI3KCA, SRC and p53, were found to exercise their effects through microRNA 135b.

This is significant because many people develop a resistance to treatments blocking bowel cancer mutations. Inhibiting microRNA 135b could attack cancer without resistance occurring by blocking the effects of multiple cancer-causing mutations simultaneously.

Testing for microRNA 135b could also identify patients who are most in need of treatment.

Professor Owen Sansom, deputy director of The Cancer Research UK Beatson Institute at Glasgow University, said: "This exciting work shows a single microRNA can control multiple pathways that go wrong in colon cancer and offers the hope that in the future this could be targeted in patients that have colon cancer."

Researchers have gained a new insight into how traumatic experiences can affect successive generations of animals.

It has long been known in psychology that traumatic experience can induce behavioural disorders that can be passed down from one generation to the next but the underlying physiological mechanisms are poorly understood.

Isabelle Mansuy, professor at ETH Zurich and the University of Zurich, has been studying the molecular processes involved in non-genetic inheritance of behavioural symptoms induced by traumatic experiences in early life.

Her team has identified micro-RNA molecules as key factors in these processes. Enzymes synthesise these RNAs from specific sections of DNA and they are then trimmed by other enzymes into mature forms.

Cells naturally contain a number of micro-RNAs, which have a number of regulatory functions, such as controlling how many copies of a particular protein are made.

The researchers studied the number and kind of micro-RNAs expressed by adult mice exposed to traumatic conditions in early life and compared them with non-traumatised mice.

It was discovered that stress changes the amount of several micro-RNAs in the blood, brain and sperm. 

A comparison with the tissues or cells of control animals found that some micro-RNAs were produced to excess, while the others were under-produced. This resulted in a misregulation of cellular processes normally controlled by these molecules.

The mice behaved markedly differently following their traumatic experiences, exhibiting depressive-like behaviour and partly losing their natural aversion to open spaces and bright light.

While the offspring of the mice were not directly affected by traumatic stress, these behavioural symptoms were passed on to the next generation via sperm.

The metabolism of these stressed mice was also affected: their insulin and blood sugar levels were found to be lower than in the offspring of non-traumatized parents, and these even persisted three generations down the line.

It is an open question how the misregulation in short RNAs occurs, but Professor Mansuy said it probably begins with the overproduction of stress hormones.

She said other traits may also be passed on through similar mechanisms. The research team is currently investigating the role of short RNAs in trauma inheritance in humans.

A research team from UC Irvine's Sue & Bill Gross Stem Cell Research Center has found that stem cells derived from bone marrow may have the potential to treat stroke victims.

Neurologist Dr Steven Cramer and biomedical engineer Weian Zhao conducted an analysis of published research, identifying 46 studies that used mesenchymal stromal cells (MSCs) in animal models of stroke.

MSCs, which are a type of multipotent adult stem cells mostly processed from bone marrow, were found to be significantly better than control therapy in 44 of the studies.

Significantly, the effects of the cells on recovery were strong irrespective of the dosage, the time the MSCs were administered relative to stroke onset or the method of administration.

MSCs were effective whether introduced via the blood or the brain, even if they were administered a month after the event.

"Stroke remains a major cause of disability, and we are encouraged that the preclinical evidence shows [MSCs'] efficacy with ischemic stroke," said Dr Cramer, a professor of neurology and leading stroke expert. 

"MSCs are of particular interest because they come from bone marrow, which is readily available, and are relatively easy to culture. In addition, they already have demonstrated value when used to treat other human diseases."

While MSCs transform into a wide variety of cell types, such as bone, cartilage and fat cells, they do not differentiate into neural cells.

The cells nevertheless play important roles in promoting brain repair following a stroke. They are attracted to injury sites and release a wide range of molecules in response to signals released by these damaged areas.

MSCs are responsible for a number of activities: blood vessel creation to enhance circulation, protection of cells starting to die and growth of brain cells, among others.

When MSCs are able to reach the bloodstream, they gather in parts of the body that control the immune system and help to create an environment that is more conducive to brain repair.

Dr Cramer said the findings could form the basis of further studies on the use of MSCs in the treatment of ischemic stroke in humans.

A discovery that adds a new drug target to cancer immunotherapy has been identified by researchers from La Jolla Institute for Allergy and Immunology and their collaborators from other institutes.

The study reveals a new way to block the function of immune inhibitory checkpoint receptor CTLA-4, which is already generating a large amount of interest in the pharmaceutical and research communities due to its cancer-fighting potential.

Led by Dr Amnon Altman and Dr Kok-Fai Kong, the team demonstrated a previously unknown interaction between CTLA-4 and an intracellular enzyme protein kinase known as C-eta.

This interaction is critical for the functioning of regulatory T cells, which suppress the immune system. 

While this activity is normally a useful part of a healthy immune system, preventing the body from potentially damaging immune responses that lead to autoimmune diseases, it can inhibit beneficial immune attacks against cancer.

CTLA-4 is a protein that is found on the surface of regulatory T-cells, where it plays an important role in immune suppression.

"The way it works is that this enzyme physically binds to the CTLA-4 receptor," said Dr Altman. "This binding is critical for certain suppressive functions of the regulatory T cells to proceed."

Dr Altman and his team found the enzyme must bind to CTLA-4 in order for the regulatory T cells to turn down the immune system in mice.

They also discovered that eliminating this enzyme prevented regulatory T cells from suppressing the immune system's response against a growing tumour.

Although regulatory T cells lacking protein kinase C-eta failed to inhibit an immune response against a growing tumour, they were able to continue to inhibit autoimmune disease in a mouse model of inflammatory bowel disease.

"This means that you could potentially create a therapy that would allow for a more effective immune response against cancer without the risk of increasing susceptibility to autoimmune diseases," said Dr Altman. 

He added that this is important as it points to an immune mechanism specific to tumours which does not result in a response that could lead to autoimmune diseases.

Dr Altman said this is possibly due to the fact that regulatory T cells use diverse means to suppress different immune responses that do not depend on the link between C-eta and CTLA-4.