Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Single microRNA causes cancer in transgenic mouse

19.04.2006
Scientists in the Ohio State University Comprehensive Cancer Center say that just one, single, malfunctioning microRNA is sufficient to cause cancer in mice. The discovery offers new insight into the development of some forms of leukemia and lymphoma and at the same time underscores the powerful role that these tiny snippets of non-coding RNA play in cell signaling pathways active in carcinogenesis.

“To the best of our knowledge, this is the first direct evidence that overexpression of a microRNA results in the development of a neoplastic disease, highlighting their potential role in human malignancies,” says Carlo Croce, director of Ohio State’s Human Cancer Genetics Program and professor and chair of the department of molecular virology, immunology and medical genetics.

Over the past several years, scientists have discovered hundreds of microRNAs (miRNAs) and how they regulate gene expression – basically, by blocking messenger RNA’s instructions for protein production. MiRNAs normally help control important biological functions by switching “on” and “off” at different times during cell growth, death, development and differentiation. They can be harmful, though, if they are activated at the wrong time in the wrong place, and that appears to be what happens in some forms of cancer.

The study is published online in the Proceedings of the National Academy of Sciences.

Croce, the senior author of the study and the first to identify a link between miRNAs and cancer, suspected that a particular miRNA, miR155, was a key culprit in some forms of malignant growth. He and his colleagues have been mapping the activity of dozens of miRNAs in various types of normal and malignant tissues for several years. Earlier studies showed that miR155 was unusually active in some types of leukemia and lymphoma, and that its presence indicated a poorer prognosis in patients with breast and lung cancers.

Croce, along with Dr. Stefan Costinean , a research associate, decided to isolate miR155 function by inserting the gene, along with an enhancer, to promote its expression, into fertilized eggs inside a pregnant mouse. The researchers then screened the offspring to find those that had incorporated miR155 into their genomes and followed them to see what effect miR155 might have.

Within three weeks, the transgenic mice developed greatly enlarged spleens, and after six to seven months, they became sick and died. Offspring that did not express miR 155 did not have enlarged spleens and developed normally.

When Costinean examined the spleens of the transgenic mice more closely, he discovered they were full of immature B cells – and only immature B cells.

“This is significant, because a proliferation of these precursor B cells is one of the hallmarks of some types of leukemia and lymphoma,” he said.

B cells, or lymphocytes, are white blood cells that help the body fight infection.

In humans, they are produced from stem cells in the bone marrow and then evolve through several stages before they become mature enough to create antibodies. Antibodies are proteins that sit on the surface of B cells or that are secreted by B cells that can detect the presence of foreign invaders like bacteria, viruses or parasites.

Lab tests revealed that the B cells in enlarged spleens had stopped evolving in the pre-B phase, right at the point where a B cell normally begins to create structures necessary for antibody development.

“We believe that miR 155 initiated the process that blocked further differentiation of these cells,” says Costinean.

Croce says the results are consistent with previous study findings. “We know that miRNAs often act just like oncogenes, in that they promote abnormal cell growth that leads to cancer. Others, however, behave more like tumor suppressors, because they block genes that keep abnormal cell division in check or induce prolonged survival. Our transgenic mouse model clearly shows that miR155 is an oncogene, because it leads to B cell malignancies when it is dysregulated.”

Although they now understand that miR 155 overexpression can lead to cancer, the researchers say they still haven’t identified the exact mechanism that makes that happen. Still, the study suggests that a newly emerging class of artificially designed molecules (called antagomirs) may be able to block miR 155 expression and be an effective therapeutic strategy in patients with acute lymphoblastic leukemia or high grade lymphomas.

The study was funded by grants from the National Cancer Institute.

Co-authors include Nicola Zanesi, a research scientist in the OSU Comprehensive Cancer Center; Yuri Pekarsky and Stefano Volinia, both assistant professors in the department of molecular virology, immunology and medical genetics; Esmerina Tili, a post-doctoral researcher in the OSU Comprehensive Cancer Center; and Nyla Heerema, a professor of pathology in the OSU College of Medicine.

Michelle Gailiun | EurekAlert!
Further information:
http://www.osumc.edu

More articles from Life Sciences:

nachricht Individual Receptors Caught at Work
19.10.2017 | Julius-Maximilians-Universität Würzburg

nachricht Rapid environmental change makes species more vulnerable to extinction
19.10.2017 | Universität Zürich

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Neutron star merger directly observed for the first time

University of Maryland researchers contribute to historic detection of gravitational waves and light created by event

On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...

Im Focus: Breaking: the first light from two neutron stars merging

Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.

Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

Im Focus: Shrinking the proton again!

Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.

It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

Climate Engineering Conference 2017 Opens in Berlin

10.10.2017 | Event News

 
Latest News

Electrode materials from the microwave oven

19.10.2017 | Materials Sciences

New material for digital memories of the future

19.10.2017 | Materials Sciences

Physics boosts artificial intelligence methods

19.10.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>