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 Cryo-electron microscopy achieves unprecedented resolution using new computational methods
24.03.2017 | DOE/Lawrence Berkeley National Laboratory

nachricht How cheetahs stay fit and healthy
24.03.2017 | Forschungsverbund Berlin e.V.

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

Im Focus: Researchers Imitate Molecular Crowding in Cells

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Argon is not the 'dope' for metallic hydrogen

24.03.2017 | Materials Sciences

Astronomers find unexpected, dust-obscured star formation in distant galaxy

24.03.2017 | Physics and Astronomy

Gravitational wave kicks monster black hole out of galactic core

24.03.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>