The study also shows that three of these miRNAs inhibit the action of two genes important for cancer development, helping to explain how the drug works.
The drug is called all-trans-retinoic acid (ATRA) and it is considered the gold standard for treating the disease.
The study showed that ATRA raises the levels of three particular miRNAs in leukemia cells and that this rise coincides with a fall in activity of two important cancer-causing genes. The three are identified as miRNA-15b, miRNA-16-1 and let-7.
Two of these, miRNA-15b and miRNA-16-1, reduce the activity of the Bcl-2 gene, which is over-active in many kinds of cancer. The protein produced by this gene blocks the normal process of cell death and helps keep cancer cells alive long after they should have died.
The remaining miRNA molecule, let-7, lowered the activity of the Ras oncogene, an important cancer-causing gene. (Oncogenes are normal genes that when mutated lead to cancer.)
Researchers at the Ohio State University Comprehensive Cancer Center led the study, which was published in a recent issue of the journal Oncogene.
“The findings are important because they tell us that some miRNAs switch off genes that promote cancer,” says first author Ramiro Garzon, a hematologist and oncologist at Ohio State's James Cancer Hospital and Solove Research Institute.
Acute promyelocytic leukemia occurs when cells that give rise to a form of white blood cell become stuck at an immature stage. The immature cells accumulate until they crowd out healthy white cells in the blood and bone marrow.
“Our findings suggest that these three miRNAs help re-program the malignant cells to a more normal state,” Garzon says, “and that they are also important for normal differentiation.”
In this study, the researchers used leukemia cells grown in the laboratory and cells donated by patients to study how the drug ATRA affects miRNA levels and how those changes affect the cells.
The investigators exposed the leukemia cells to the drug for up to 96 hours, causing the cells to mature. The treatment increased the level of eight miRNAs and a drop in one compared with untreated cells.
Of these, the researchers focused on miRNA-15b and miRNA-16-1, which are known to regulate the activity of the Bcl-2 gene. They found that high levels of the two miRNAs were associated with low Bcl-2 activity.
Next, they showed that the two miRNAs actually caused the drop in Bcl-2 activity. They did this by adding additional amounts of the two miRNAs to leukemia cells not treated with ATRA. Restoring the miRNAs caused a strong drop in Bcl-2 levels.
The researchers then looked at miRNA let-7, a known regulator of the Ras oncogene, and likewise found that high levels of this miRNA were associated with low Ras activity.
They established a cause and effect relationship as before, by adding additional let-7 to untreated leukemia cells.
“Overall,” Garzon says, “our findings show that ATRA induces the expression of these three miRNAs, and through them regulates genes that need to be silenced for the cell to differentiate.”
Funding from the National Cancer Institute, the Paul and Mary Haas Chair in Genetics, a Lauri Strauss Discovery grant award, the Kimmel Foundation and the CLL Global Research Foundation supported this research.
Jacqueline Weaver | EurekAlert!
Complementing conventional antibiotics
24.05.2018 | Goethe-Universität Frankfurt am Main
Building a brain, cell by cell: Researchers make a mini neuron network (of two)
23.05.2018 | Institute of Industrial Science, The University of Tokyo
A research team led by physicists at the Technical University of Munich (TUM) has developed molecular nanoswitches that can be toggled between two structurally different states using an applied voltage. They can serve as the basis for a pioneering class of devices that could replace silicon-based components with organic molecules.
The development of new electronic technologies drives the incessant reduction of functional component sizes. In the context of an international collaborative...
At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.
At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...
There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?
At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...
So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics
Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...
The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...
02.05.2018 | Event News
13.04.2018 | Event News
12.04.2018 | Event News
24.05.2018 | Ecology, The Environment and Conservation
24.05.2018 | Medical Engineering
24.05.2018 | Physics and Astronomy