Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

miR loss may power maligant transformation in chronic leukemia

06.07.2012
Loss of a particular microRNA in chronic lymphocytic leukemia shuts down normal cell metabolism and turns up alternative mechanisms that enable cancer cells to produce the energy and build the molecules they need to proliferate and invade neighboring tissue.
The findings come from a new study led by researchers at the Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James).

The study shows that microRNA-125b (miR-125b) by itself regulates many enzymes and other molecules that allow cells to make building blocks needed for their growth and proliferation such as DNA and lipids needed for cell membranes.

It also shows that miR-125b is often lost in chronic lymphocytic leukemia (CLL), and that the loss is associated with higher rates of glucose metabolism. This is a characteristic of cancer cells called the Warburg effect, and it alters how cancer cells use sugar (glucose) to generate energy. This finding suggests that loss of miR-125b is an early step in CLL development.

The findings, published in the journal Blood, provide a more comprehensive understanding of how cancer develops and identifies new potential targets for CLL drug development, the researchers say.

"Our findings indicate that miR-125b is downregulated in both aggressive and indolent forms of CLL, and that this downregulation is associated with metabolic adaptation to cancer transformation," says principal investigator and corresponding author Dr. Carlo Croce, director of Ohio State's Human Cancer Genetics program and a member of the OSUCCC – James Molecular Biology and Cancer Genetics program.

"By identifying the metabolites that are changed, as we have here, we can propose to use drugs that target them and perhaps control the leukemia," Croce says.

Scientists have known for some time that, as normal cells become cancer cells, different metabolic pathways are switched on and support the enhanced growth and energy needs that malignant cells require. This study reveals one new way that that can happen.

"The power of microRNAs is that they simultaneously control the expression of many genes, usually by suppressing them," says co-corresponding author Esmerina Tili, who is also first author and a post-doctoral researcher in Croce's laboratory.

"We believe miR-125b is a master regulator of cell metabolism, and that its loss enhances metabolism and leads to a transformed state," Tili says. "As the level of miR-125b goes down in CLL cells, the levels of many of the molecules it controls go up, enabling rapid cell growth."

These molecules, along with miR-125b itself, warrant further investigation as possible targets for new drugs to control CLL progression, she says.

"Cancer is a complex disease," Croce says. "The more we know about the changes that occur when cells become malignant, the better therapies we can design."

Funding from the NIH/National Cancer Institute (grant CA151319) supported this research.

Other researchers involved in this study were Zhenghua Luo and Stefano Volinia of The Ohio State University; Jean-Jacques Michaille of Université de Bourgogne, Faculté Gabriel, Dijon, France, who has regularly conducted research at Ohio State University since 2005; and Laura Z. Rassenti and Thomas J. Kipps of Moores Universary of California San Diego Cancer Center.

The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute strives to create a cancer-free world by integrating scientific research with excellence in education and patient-centered care, a strategy that leads to better methods of prevention, detection and treatment. Ohio State is one of only 41 National Cancer Institute (NCI)-designated Comprehensive Cancer Centers and one of only seven centers funded by the NCI to conduct both phase I and phase II clinical trials. The NCI recently rated Ohio State's cancer program as "exceptional," the highest rating given by NCI survey teams. As the cancer program's 210-bed adult patient-care component, The James is a "Top Hospital" as named by the Leapfrog Group and one of the top 20 cancer hospitals in the nation as ranked by U.S.News & World Report.

Darrell E. Ward | EurekAlert!
Further information:
http://www.osumc.edu

More articles from Health and Medicine:

nachricht Finnish research group discovers a new immune system regulator
23.02.2018 | University of Turku

nachricht Minimising risks of transplants
22.02.2018 | Friedrich-Alexander-Universität Erlangen-Nürnberg

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Attoseconds break into atomic interior

A newly developed laser technology has enabled physicists in the Laboratory for Attosecond Physics (jointly run by LMU Munich and the Max Planck Institute of Quantum Optics) to generate attosecond bursts of high-energy photons of unprecedented intensity. This has made it possible to observe the interaction of multiple photons in a single such pulse with electrons in the inner orbital shell of an atom.

In order to observe the ultrafast electron motion in the inner shells of atoms with short light pulses, the pulses must not only be ultrashort, but very...

Im Focus: Good vibrations feel the force

A group of researchers led by Andrea Cavalleri at the Max Planck Institute for Structure and Dynamics of Matter (MPSD) in Hamburg has demonstrated a new method enabling precise measurements of the interatomic forces that hold crystalline solids together. The paper Probing the Interatomic Potential of Solids by Strong-Field Nonlinear Phononics, published online in Nature, explains how a terahertz-frequency laser pulse can drive very large deformations of the crystal.

By measuring the highly unusual atomic trajectories under extreme electromagnetic transients, the MPSD group could reconstruct how rigid the atomic bonds are...

Im Focus: Developing reliable quantum computers

International research team makes important step on the path to solving certification problems

Quantum computers may one day solve algorithmic problems which even the biggest supercomputers today can’t manage. But how do you test a quantum computer to...

Im Focus: In best circles: First integrated circuit from self-assembled polymer

For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.

In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...

Im Focus: Demonstration of a single molecule piezoelectric effect

Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale

Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

2nd International Conference on High Temperature Shape Memory Alloys (HTSMAs)

15.02.2018 | Event News

Aachen DC Grid Summit 2018

13.02.2018 | Event News

How Global Climate Policy Can Learn from the Energy Transition

12.02.2018 | Event News

 
Latest News

Basque researchers turn light upside down

23.02.2018 | Physics and Astronomy

Finnish research group discovers a new immune system regulator

23.02.2018 | Health and Medicine

Attoseconds break into atomic interior

23.02.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>