Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Rare mutation causes early heart disease and metabolic syndrome

05.03.2007
New research shows that a form of vitamin A used to treat acute promyelocytic leukemia induces changes in an unusual class of small molecules called microRNAs (miRNAs) in the leukemic cells.

The study also shows that three of these miRNAs inhibit the action of two genes important for cancer development, helping to explain how the drug works.

The drug is called all-trans-retinoic acid (ATRA) and it is considered the gold standard for treating the disease.

The study showed that ATRA raises the levels of three particular miRNAs in leukemia cells and that this rise coincides with a fall in activity of two important cancer-causing genes. The three are identified as miRNA-15b, miRNA-16-1 and let-7.

... more about:
»ATRA »Bcl-2 »let-7 »leukemia »miRNA

Two of these, miRNA-15b and miRNA-16-1, reduce the activity of the Bcl-2 gene, which is over-active in many kinds of cancer. The protein produced by this gene blocks the normal process of cell death and helps keep cancer cells alive long after they should have died.

The remaining miRNA molecule, let-7, lowered the activity of the Ras oncogene, an important cancer-causing gene. (Oncogenes are normal genes that when mutated lead to cancer.)

Researchers at the Ohio State University Comprehensive Cancer Center led the study, which was published in a recent issue of the journal Oncogene.

“The findings are important because they tell us that some miRNAs switch off genes that promote cancer,” says first author Ramiro Garzon, a hematologist and oncologist at Ohio State's James Cancer Hospital and Solove Research Institute.

Acute promyelocytic leukemia occurs when cells that give rise to a form of white blood cell become stuck at an immature stage. The immature cells accumulate until they crowd out healthy white cells in the blood and bone marrow.

“Our findings suggest that these three miRNAs help re-program the malignant cells to a more normal state,” Garzon says, “and that they are also important for normal differentiation.”

In this study, the researchers used leukemia cells grown in the laboratory and cells donated by patients to study how the drug ATRA affects miRNA levels and how those changes affect the cells.

The investigators exposed the leukemia cells to the drug for up to 96 hours, causing the cells to mature. The treatment increased the level of eight miRNAs and a drop in one compared with untreated cells.

Of these, the researchers focused on miRNA-15b and miRNA-16-1, which are known to regulate the activity of the Bcl-2 gene. They found that high levels of the two miRNAs were associated with low Bcl-2 activity.

Next, they showed that the two miRNAs actually caused the drop in Bcl-2 activity. They did this by adding additional amounts of the two miRNAs to leukemia cells not treated with ATRA. Restoring the miRNAs caused a strong drop in Bcl-2 levels.

The researchers then looked at miRNA let-7, a known regulator of the Ras oncogene, and likewise found that high levels of this miRNA were associated with low Ras activity.

They established a cause and effect relationship as before, by adding additional let-7 to untreated leukemia cells.

“Overall,” Garzon says, “our findings show that ATRA induces the expression of these three miRNAs, and through them regulates genes that need to be silenced for the cell to differentiate.”

Funding from the National Cancer Institute, the Paul and Mary Haas Chair in Genetics, a Lauri Strauss Discovery grant award, the Kimmel Foundation and the CLL Global Research Foundation supported this research.

Jacqueline Weaver | EurekAlert!
Further information:
http://www.yale.edu

Further reports about: ATRA Bcl-2 let-7 leukemia miRNA

More articles from Life Sciences:

nachricht Scientists uncover the role of a protein in production & survival of myelin-forming cells
19.07.2018 | Advanced Science Research Center, GC/CUNY

nachricht NYSCF researchers develop novel bioengineering technique for personalized bone grafts
18.07.2018 | New York Stem Cell Foundation

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: First evidence on the source of extragalactic particles

For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.

To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.

Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...

Im Focus: Breaking the bond: To take part or not?

Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.

A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...

Im Focus: New 2D Spectroscopy Methods

Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.

"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....

Im Focus: Chemical reactions in the light of ultrashort X-ray pulses from free-electron lasers

Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.

Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

Metal too 'gummy' to cut? Draw on it with a Sharpie or glue stick, science says

19.07.2018 | Materials Sciences

NSF-supported researchers to present new results on hurricanes and other extreme events

19.07.2018 | Earth Sciences

Scientists uncover the role of a protein in production & survival of myelin-forming cells

19.07.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>