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!
North and South Cooperation to Combat Tuberculosis
22.03.2018 | Universität Zürich
Researchers Discover New Anti-Cancer Protein
22.03.2018 | Universität Basel
An international team of researchers has discovered a new anti-cancer protein. The protein, called LHPP, prevents the uncontrolled proliferation of cancer cells in the liver. The researchers led by Prof. Michael N. Hall from the Biozentrum, University of Basel, report in “Nature” that LHPP can also serve as a biomarker for the diagnosis and prognosis of liver cancer.
The incidence of liver cancer, also known as hepatocellular carcinoma, is steadily increasing. In the last twenty years, the number of cases has almost doubled...
In just a few weeks from now, the Chinese space station Tiangong-1 will re-enter the Earth's atmosphere where it will to a large extent burn up. It is possible that some debris will reach the Earth's surface. Tiangong-1 is orbiting the Earth uncontrolled at a speed of approx. 29,000 km/h.Currently the prognosis relating to the time of impact currently lies within a window of several days. The scientists at Fraunhofer FHR have already been monitoring Tiangong-1 for a number of weeks with their TIRA system, one of the most powerful space observation radars in the world, with a view to supporting the German Space Situational Awareness Center and the ESA with their re-entry forecasts.
Following the loss of radio contact with Tiangong-1 in 2016 and due to the low orbital height, it is now inevitable that the Chinese space station will...
Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP, provider of research and development services for OLED lighting solutions, announces the founding of the “OLED Licht Forum” and presents latest OLED design and lighting solutions during light+building, from March 18th – 23rd, 2018 in Frankfurt a.M./Germany, at booth no. F91 in Hall 4.0.
They are united in their passion for OLED (organic light emitting diodes) lighting with all of its unique facets and application possibilities. Thus experts in...
A new scenario seeking to explain how Mars' putative oceans came and went over the last 4 billion years implies that the oceans formed several hundred million...
For the first time, an interdisciplinary team from the University of Basel has succeeded in integrating artificial organelles into the cells of live zebrafish embryos. This innovative approach using artificial organelles as cellular implants offers new potential in treating a range of diseases, as the authors report in an article published in Nature Communications.
In the cells of higher organisms, organelles such as the nucleus or mitochondria perform a range of complex functions necessary for life. In the networks of...
19.03.2018 | Event News
16.03.2018 | Event News
13.03.2018 | Event News
22.03.2018 | Trade Fair News
22.03.2018 | Earth Sciences
22.03.2018 | Earth Sciences