Targeted therapies are a growing and groundbreaking field in cancer care in which drugs or other substances are designed to interfere with genes or molecules that control the growth and survival of cancer cells.
Now, scientists at Virginia Commonwealth University Massey Cancer Center and VCU Institute of Molecular Medicine (VIMM) have identified a novel interaction between a microRNA and a gene that could lead to new therapies for the most common and deadly form of brain tumor, malignant glioma.
In a study recently published in the journal Neuro-Oncology, a team of scientists led by Luni Emdad, M.B.B.S., Ph.D., and Paul B. Fisher, M.Ph., Ph.D., provided the first evidence of an important link between a specific microRNA, miR-184, and a cancer promoting gene, SND1, in the regulation of malignant glioma. miR-184 is known to suppress tumor development by regulating a variety of genes involved in cancer growth, while SND1 has been shown to play a significant role in the development of breast, colon, prostate and liver cancers.
Through a variety of preclinical experiments, the team demonstrated that increasing the expression of miR-184 slows the growth and invasive characteristics of glioma cells through direct regulation of SND1. Additionally, they showed that reduced levels of SND1 led to reduced levels of STAT3, a gene that has been shown to promote the most lethal characteristics of brain cancer.
"Patients suffering from brain tumors are in desperate need of improved therapies," says Fisher, Thelma Newmeyer Corman Endowed Chair in Cancer Research and co-leader of the Cancer Molecular Genetics research program at VCU Massey Cancer Center, chairman of the Department of Human and Molecular Genetics at VCU School of Medicine and director of the VIMM. "We're hopeful that this new understanding of the relationship between miR-184 and SND1 ultimately will lead to the development of new drugs that reduce SND1 expression and improve patient outcomes."
Prior studies have shown that levels of miR-184 are unusually low in tissue samples from patients with malignant gliomas. Using advanced computer analysis techniques designed to study and process biological data, the researchers identified SND1 among a handful of other genes that miR-184 helps regulate. Knowing SND1 is implicated in a variety of cancers and having previously defined its role in liver cancer, Emdad, Fisher and their colleagues explored this relationship further.
They confirmed low levels of miR-184 expression in human glioma tissue samples and cultured cell lines as well as an increase in the expression of SND1 compared to normal brain tissue. Using data from a large public brain tumor database called REMBRANDT, the researchers confirmed that patients with lower levels of SND1 survived longer than those with elevated SND1 expression.
"We still have a long way to go and many challenges to overcome before we will have therapies that are ready for clinical use, but this is a significant first step in the process," says Emdad, member of the Cancer Molecular Genetics research program at Massey, assistant professor in the VCU Department of Human and Molecular Genetics and member of the VIMM. "Future studies will aim to explore the relationship between SND1 and STAT3, identify additional microRNAs that may be relevant to malignant glioma and explore the effects of drugs that block SND1 expression in more advanced preclinical models."
Fisher and Emdad collaborated with Devanand Sarkar, M.B.B.S., Ph.D., Harrison Scholar and member of the Cancer Molecular Genetics research program at Massey, Blick Scholar and associate professor in the Department of Human and Molecular Genetics at the VCU School of Medicine and member of the VIMM; Swadesh K. Das, Ph.D., member of the Cancer Molecular Genetics research program at Massey, member of the VIMM and assistant professor in the VCU Department of Human and Molecular Genetics; Mitchell E. Menezes, Ph.D., Prasanna K. Santhekadur, Ph.D., and Bin Hu, Ph.D., all postdoctoral research scientists in the VCU Department of Human and Molecular Genetics; and Aleksandar Janjic, Mohammad Al-Zubi and Xue-Ning Shen, all research technicians in the VCU Department of Human and Molecular Genetics and the VIMM.
The full manuscript of this study is available online at: http://www.ncbi.nlm.nih.gov/pubmed/25216670 .
John Wallace | EurekAlert!
GLUT5 fluorescent probe fingerprints cancer cells
20.04.2018 | Michigan Technological University
Scientists re-create brain neurons to study obesity and personalize treatment
20.04.2018 | Cedars-Sinai Medical Center
University of Connecticut researchers have created a biodegradable composite made of silk fibers that can be used to repair broken load-bearing bones without the complications sometimes presented by other materials.
Repairing major load-bearing bones such as those in the leg can be a long and uncomfortable process.
Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.
Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...
Novel highly efficient and brilliant gamma-ray source: Based on model calculations, physicists of the Max PIanck Institute for Nuclear Physics in Heidelberg propose a novel method for an efficient high-brilliance gamma-ray source. A giant collimated gamma-ray pulse is generated from the interaction of a dense ultra-relativistic electron beam with a thin solid conductor. Energetic gamma-rays are copiously produced as the electron beam splits into filaments while propagating across the conductor. The resulting gamma-ray energy and flux enable novel experiments in nuclear and fundamental physics.
The typical wavelength of light interacting with an object of the microcosm scales with the size of this object. For atoms, this ranges from visible light to...
Stable joint cartilage can be produced from adult stem cells originating from bone marrow. This is made possible by inducing specific molecular processes occurring during embryonic cartilage formation, as researchers from the University and University Hospital of Basel report in the scientific journal PNAS.
Certain mesenchymal stem/stromal cells from the bone marrow of adults are considered extremely promising for skeletal tissue regeneration. These adult stem...
In the fight against cancer, scientists are developing new drugs to hit tumor cells at so far unused weak points. Such a “sore spot” is the protein complex...
13.04.2018 | Event News
12.04.2018 | Event News
09.04.2018 | Event News
20.04.2018 | Physics and Astronomy
20.04.2018 | Interdisciplinary Research
20.04.2018 | Physics and Astronomy