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 Diabetes mellitus: A risk factor for early colorectal cancer
27.05.2020 | Nationales Centrum für Tumorerkrankungen (NCT) Heidelberg

nachricht Ultra-thin fibres designed to protect nerves after brain surgery
27.05.2020 | Martin-Luther-Universität Halle-Wittenberg

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: Biotechnology: Triggered by light, a novel way to switch on an enzyme

In living cells, enzymes drive biochemical metabolic processes enabling reactions to take place efficiently. It is this very ability which allows them to be used as catalysts in biotechnology, for example to create chemical products such as pharmaceutics. Researchers now identified an enzyme that, when illuminated with blue light, becomes catalytically active and initiates a reaction that was previously unknown in enzymatics. The study was published in "Nature Communications".

Enzymes: they are the central drivers for biochemical metabolic processes in every living cell, enabling reactions to take place efficiently. It is this very...

Im Focus: New double-contrast technique picks up small tumors on MRI

Early detection of tumors is extremely important in treating cancer. A new technique developed by researchers at the University of California, Davis offers a significant advance in using magnetic resonance imaging to pick out even very small tumors from normal tissue. The work is published May 25 in the journal Nature Nanotechnology.

researchers at the University of California, Davis offers a significant advance in using magnetic resonance imaging to pick out even very small tumors from...

Im Focus: I-call - When microimplants communicate with each other / Innovation driver digitization - "Smart Health“

Microelectronics as a key technology enables numerous innovations in the field of intelligent medical technology. The Fraunhofer Institute for Biomedical Engineering IBMT coordinates the BMBF cooperative project "I-call" realizing the first electronic system for ultrasound-based, safe and interference-resistant data transmission between implants in the human body.

When microelectronic systems are used for medical applications, they have to meet high requirements in terms of biocompatibility, reliability, energy...

Im Focus: When predictions of theoretical chemists become reality

Thomas Heine, Professor of Theoretical Chemistry at TU Dresden, together with his team, first predicted a topological 2D polymer in 2019. Only one year later, an international team led by Italian researchers was able to synthesize these materials and experimentally prove their topological properties. For the renowned journal Nature Materials, this was the occasion to invite Thomas Heine to a News and Views article, which was published this week. Under the title "Making 2D Topological Polymers a reality" Prof. Heine describes how his theory became a reality.

Ultrathin materials are extremely interesting as building blocks for next generation nano electronic devices, as it is much easier to make circuits and other...

Im Focus: Rolling into the deep

Scientists took a leukocyte as the blueprint and developed a microrobot that has the size, shape and moving capabilities of a white blood cell. Simulating a blood vessel in a laboratory setting, they succeeded in magnetically navigating the ball-shaped microroller through this dynamic and dense environment. The drug-delivery vehicle withstood the simulated blood flow, pushing the developments in targeted drug delivery a step further: inside the body, there is no better access route to all tissues and organs than the circulatory system. A robot that could actually travel through this finely woven web would revolutionize the minimally-invasive treatment of illnesses.

A team of scientists from the Max Planck Institute for Intelligent Systems (MPI-IS) in Stuttgart invented a tiny microrobot that resembles a white blood cell...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Dresden Nexus Conference 2020: Same Time, Virtual Format, Registration Opened

19.05.2020 | Event News

Aachen Machine Tool Colloquium AWK'21 will take place on June 10 and 11, 2021

07.04.2020 | Event News

International Coral Reef Symposium in Bremen Postponed by a Year

06.04.2020 | Event News

 
Latest News

Black nitrogen: Bayreuth researchers discover new high-pressure material and solve a puzzle of the periodic table

29.05.2020 | Materials Sciences

Argonne researchers create active material out of microscopic spinning particles

29.05.2020 | Materials Sciences

Smart windows that self-illuminate on rainy days

29.05.2020 | Power and Electrical Engineering

VideoLinks
Science & Research
Overview of more VideoLinks >>>