The research, using human chronic lymphocytic leukemia (CLL) cells, also showed that loss of the two molecules affects 70 genes, most of which are involved in critical functions such as cell growth, death, proliferation and metabolism.
The findings reveal how the two molecules, called miR-15a and miR-16-1, normally protect against cancer, and suggest a possible new treatment strategy for CLL.
The study, led by researchers at the Ohio State University Comprehensive Cancer Center, was published recently in the Proceedings of the National Academy of Sciences.
“These findings give us a signature of 70 deregulated genes that we believe finally explains at the molecular level how these two molecules contribute to CLL,” says principal investigator Carlo M. Croce, director of Ohio State’s human cancer genetics program.
“The identification of these genes could also have important significance for the development of new therapeutic approaches for chronic leukemias.”
The two molecules are forms of microRNA, tiny molecules that cells use to help regulate the type and amount of proteins they make.
In 2005, Croce and his colleagues first showed that these two microRNAs target a gene called Bcl2, which normally helps cells survive by protecting them from accidental self-destruction. In CLL, however, the gene behaves abnormally and helps the leukemic cells survive long after they should have died.
Croce and his colleagues believe that loss of the two molecules alters the gene’s behavior.
For the new study, the investigators first injected mice with leukemia cells in which they had restored the two microRNAs. This completely suppressed tumor growth in three of five animals. Mice injected with leukemic cells that lacked the two molecules, on the other hand, developed significant tumors.
“This clearly showed that these two microRNAs can suppress tumor development,” says coauthor Muller Fabrri, a researcher in Croce’s laboratory.
Because each microRNA regulates many genes, the investigators wanted to learn which ones, in addition to Bcl2, are affected in cells lacking the two molecules.
First, they measured differences in gene activity in laboratory-grown CLL cells that had either high or low levels of the two molecules.
Next, they measured the levels of all the proteins in the two groups of cells. This proteomic analysis revealed 27 proteins with highly altered amounts. These were identified and shown to be involved in cell growth, cell death and cancer development.
Last, the researchers used human CLL cells from 16 patients to verify the gene targets.
“Together, these extensive experiments revealed the signature of 70 genes controlled by the two microRNAs,” Fabbri says. “They show that microRNAs can affect different biochemical pathways in different ways, and they explain at the molecular level what these two miRNAs do in this disease.”
Darrell E. Ward | EurekAlert!
Colorectal cancer: Increased life expectancy thanks to individualised therapies
20.02.2020 | Christian-Albrechts-Universität zu Kiel
Sweet beaks: What Galapagos finches and marine bacteria have in common
20.02.2020 | Max-Planck-Institut für Marine Mikrobiologie
The operational speed of semiconductors in various electronic and optoelectronic devices is limited to several gigahertz (a billion oscillations per second). This constrains the upper limit of the operational speed of computing. Now researchers from the Max Planck Institute for the Structure and Dynamics of Matter in Hamburg, Germany, and the Indian Institute of Technology in Bombay have explained how these processes can be sped up through the use of light waves and defected solid materials.
Light waves perform several hundred trillion oscillations per second. Hence, it is natural to envision employing light oscillations to drive the electronic...
Most natural and artificial surfaces are rough: metals and even glasses that appear smooth to the naked eye can look like jagged mountain ranges under the microscope. There is currently no uniform theory about the origin of this roughness despite it being observed on all scales, from the atomic to the tectonic. Scientists suspect that the rough surface is formed by irreversible plastic deformation that occurs in many processes of mechanical machining of components such as milling.
Prof. Dr. Lars Pastewka from the Simulation group at the Department of Microsystems Engineering at the University of Freiburg and his team have simulated such...
Investigation of the temperature dependence of the skyrmion Hall effect reveals further insights into possible new data storage devices
The joint research project of Johannes Gutenberg University Mainz (JGU) and the Massachusetts Institute of Technology (MIT) that had previously demonstrated...
Researchers at Chalmers University of Technology, Sweden, recently completed a 5-year research project looking at how to make fibre optic communications systems more energy efficient. Among their proposals are smart, error-correcting data chip circuits, which they refined to be 10 times less energy consumptive. The project has yielded several scientific articles, in publications including Nature Communications.
Streaming films and music, scrolling through social media, and using cloud-based storage services are everyday activities now.
After helping develop a new approach for organic synthesis -- carbon-hydrogen functionalization -- scientists at Emory University are now showing how this approach may apply to drug discovery. Nature Catalysis published their most recent work -- a streamlined process for making a three-dimensional scaffold of keen interest to the pharmaceutical industry.
"Our tools open up whole new chemical space for potential drug targets," says Huw Davies, Emory professor of organic chemistry and senior author of the paper.
12.02.2020 | Event News
16.01.2020 | Event News
15.01.2020 | Event News
21.02.2020 | Medical Engineering
21.02.2020 | Health and Medicine
21.02.2020 | Physics and Astronomy