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 New method uses just a drop of blood to monitor lung cancer treatment
19.10.2018 | Osaka University

nachricht Photoactive bacteria bait may help in fight against MRSA infections
12.10.2018 | Purdue University

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: Goodbye, silicon? On the way to new electronic materials with metal-organic networks

Scientists at the Max Planck Institute for Polymer Research (MPI-P) in Mainz (Germany) together with scientists from Dresden, Leipzig, Sofia (Bulgaria) and Madrid (Spain) have now developed and characterized a novel, metal-organic material which displays electrical properties mimicking those of highly crystalline silicon. The material which can easily be fabricated at room temperature could serve as a replacement for expensive conventional inorganic materials used in optoelectronics.

Silicon, a so called semiconductor, is currently widely employed for the development of components such as solar cells, LEDs or computer chips. High purity...

Im Focus: Storage & Transport of highly volatile Gases made safer & cheaper by the use of “Kinetic Trapping"

Augsburg chemists present a new technology for compressing, storing and transporting highly volatile gases in porous frameworks/New prospects for gas-powered vehicles

Storage of highly volatile gases has always been a major technological challenge, not least for use in the automotive sector, for, for example, methane or...

Im Focus: Disrupting crystalline order to restore superfluidity

When we put water in a freezer, water molecules crystallize and form ice. This change from one phase of matter to another is called a phase transition. While this transition, and countless others that occur in nature, typically takes place at the same fixed conditions, such as the freezing point, one can ask how it can be influenced in a controlled way.

We are all familiar with such control of the freezing transition, as it is an essential ingredient in the art of making a sorbet or a slushy. To make a cold...

Im Focus: Micro energy harvesters for the Internet of Things

Fraunhofer IWS Dresden scientists print electronic layers with polymer ink

Thin organic layers provide machines and equipment with new functions. They enable, for example, tiny energy recuperators. In future, these will be installed...

Im Focus: Dynamik einzelner Proteine

Neue Messmethode erlaubt es Forschenden, die Bewegung von Molekülen lange und genau zu verfolgen

Das Zusammenspiel aus Struktur und Dynamik bestimmt die Funktion von Proteinen, den molekularen Werkzeugen der Zelle. Durch Fortschritte in der...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Conference to pave the way for new therapies

17.10.2018 | Event News

Berlin5GWeek: Private industrial networks and temporary 5G connectivity islands

16.10.2018 | Event News

5th International Conference on Cellular Materials (CellMAT), Scientific Programme online

02.10.2018 | Event News

 
Latest News

Nanocages in the lab and in the computer: how DNA-based dendrimers transport nanoparticles

19.10.2018 | Life Sciences

Thin films from Braunschweig on the way to Mercury

19.10.2018 | Physics and Astronomy

App-App-Hooray! - Innovative Kits for AR Applications

19.10.2018 | Trade Fair News

VideoLinks
Science & Research
Overview of more VideoLinks >>>