PRESS-NEWS.org - Press Release Distribution
FREE PRESS RELEASES DISTRIBUTION

Scripps Research Institute study shows microRNAs can trigger lymphomas

2013-08-09
(Press-News.org) LA JOLLA, CA—August 8, 2012—A small group of immune-regulating molecules, when overproduced even moderately, can trigger the blood cancers known as lymphomas, according to a new study led by scientists from The Scripps Research Institute (TSRI).

The six "microRNA" molecules were already known to be overproduced in lymphomas and in many other human cancers, but no one had demonstrated that they can be the prime cause of such cancers—until now. The new study also identified the major biological pathways through which these microRNAs ignite and maintain cancerous growth.

"We were able to show how this microRNA cluster can be the main driver of cancer, and so we now can start to think about therapies to combat its effects," said TSRI Assistant Professor Changchun Xiao. Xiao was the senior investigator for the study, which appeared this week in an advance online version of the EMBO Journal, a publication of the European Molecular Biology Organization.

'Dimmer Switches'

Discovered only in the 1990s, microRNAs are short molecules that work within virtually all animal and plant cells. Typically each one functions as a "dimmer switch" for one or more genes; it binds to the transcripts of those genes and effectively keeps them from being translated into proteins. In this way microRNAs can regulate a wide variety of cellular processes.

The focus of the new study was a cluster of six microRNAs known as miR-17~92, encoded by a single gene on chromosome 13. Studies of miR-17~92, including one from Xiao's lab earlier this year, have shown that it controls various immune-related and developmental processes, depending on the type of cell in which it is expressed.

But the miR-17~92 cluster is best known as a suspected cause of cancers, so much so that it has been dubbed "oncomir-1." Since 2005, scientists have found the cluster to be overproduced in lymphomas, leukemias, brain cancers, breast cancers, prostate cancers and other tumor types. It appears to play an especially prominent role in lymphomas. In a study reported last year, National Cancer Institute researchers found a drastic overexpression of the miR-17~92 cluster in every tumor they sampled from patients with a common type of non-Hodgkin's lymphoma called Burkitt lymphoma.

Researchers have found evidence that this overexpression of miR-17~92 isn't merely an incidental result of cancerous change in cells; it also works to speed up cancerous growth. "What hasn't been known is whether miR-17~92 can be the primary trigger of such cancers," said Xiao.

Identifying a Primary Trigger for Cancer

In the new study, he and his colleagues demonstrated that it can be. The project started with a colony of genetically engineered mice that Xiao established several years ago, while doing postdoctoral research in the laboratory of renowned immunologist Klaus Rajewsky at Harvard Medical School. "The mice contain an artificial gene segment that we can activate to overproduce miR-17~92 in any chosen cell type," explained Xiao. In this case, the overproduction occurs only in antibody-producing immune cells called B cells—the same cells from which Burkitt lymphoma originates.

After moving to TSRI to set up his own laboratory in 2008, Xiao expanded this transgenic mouse colony and began to gather data on it. "We found that 80 percent of these mice develop lymphomas within one year," said Hyun-Yong Jin, a graduate student in the Xiao laboratory who was a lead author of the new study.

"It was striking that this very high rate of lymphoma came from only a three-to-fivefold overexpression of miR-17~92 in B cells, whereas human Burkitt lymphomas typically show more than tenfold overexpression," Xiao said.

Having established that miR-17~92 overexpression can powerfully trigger B cell lymphomas, Xiao and his colleagues looked at this microRNA cluster's role in a standard mouse model of Burkitt lymphoma. The B cells of these mice are engineered to overexpress a cancer-inducing "oncogene" called myc, whose hyperactivity—a characteristic of human Burkitt lymphoma cases—triggers a number of abnormalities, including the overproduction of miR-17~92.

The miR-17~92 overproduction turned out to be crucial for the development of these lymphomas. "Deleting miR-17~92 from the B cells of these mice significantly delayed the development of lymphomas and extended the mice's survival," said Maoyi Lai, a research associate in the Xiao laboratory who was a lead author of the study with Hiroyo Oda, a research associate in the Xiao laboratory during the study and now a member of the National Center for Global Health and Medicine in Chiba, Japan. "Looking more closely, we found that the lymphomas that did develop in these mice originated only from B cells in which miR-17~92 had managed to escape deletion and was still being overproduced."

Taking Off the Brakes

The next step was to investigate how miR-17~92 triggers cancer so powerfully. Using a new technique for finding the binding sites of microRNAs on messenger RNAs, Xiao's collaborator Bryan R. Cullen and colleagues at the Duke University School of Medicine identified hundreds of genes that miR-17~92 works to suppress. A large fraction of these turned out to be genes that normally keep the brakes on cell growth and survival programs. By suppressing these braking genes, miR-17~92 ends up strongly promoting cell growth and survival.

"It affects so many important pathways that even a modest miR-17~92 overexpression apparently moves the cell from a normal growth and survival mode into the cancerous state," Xiao said.

Xiao's team demonstrated the importance of two of these growth/survival pathways by injecting chemical inhibitors of the pathways into mice with miR-17~92-driven lymphomas. "Each inhibitor shrank the tumors and prolonged mouse survival," said Xiao. "We're now studying the effect of combining inhibitors of these miR-17~92-driven cancer pathways and possibly targeting miR-17~92 microRNAs directly."



INFORMATION:

Contributors to the study, "MicroRNA-17~92 plays a causative role in lymphomagenesis by coordinating multiple oncogenic pathways," included Bryan R. Cullen and his postdoctoral fellow Rebecca L. Skalsky at Duke University School of Medicine; Klaus Rajewsky of Harvard Medical School (now at the Max Delbrück Center for Molecular Medicine in Berlin); Kelly Bethel of Scripps Clinic in La Jolla, CA, who performed the pathology studies of mouse lymphomas; and Jovan Shepherd, Seung Goo Kang, Wen-Hsien Liu and Mohsen Sabouri-Ghomi of the Xiao laboratory at TSRI. For more information on the paper, see http://www.nature.com/emboj/journal/vaop/ncurrent/full/emboj2013178a.html

The study was funded by the PEW Charitable Trusts, the Cancer Research Institute, and the National Institutes of Health (R01 AI067968, R01 AI087634 and RC1 CA146299).



ELSE PRESS RELEASES FROM THIS DATE:

HSCI researchers extend human epigenomic map

2013-08-09
Ten years ago, scientists announced the end of the Human Genome Project, the international attempt to learn which combination of four nucleotides—adenine, thymine, cytosine, and guanine—is unique to homo sapien DNA. This biological alphabet helped researchers identify the approximately 25,000 genes coded in the human genome, but as time went on, questions arose about how all of these genes are controlled. Now, Harvard Stem Cell Institute Principal Faculty member Alexander Meissner, PhD, reports another milestone, this time contributing to the multilayered NIH-funded human ...

A path to better MTV-MOFs

2013-08-09
Scientists would like to apply the same principles by which baking soda removes food odors from refrigerators or silica powder keeps moisture away from electronic devices to scrub carbon dioxide from the exhaust gases of fossil fuel power plants. An excellent candidate for this task is the class of materials known as multivariate metal organic frameworks or MTV-MOFs, which were discovered by Omar Yaghi, one of the world's most cited chemists. However, finding and synthesizing the best MTV-MOFs for this task has been a major challenge. That discouraging state-of-affairs ...

Hubble Space Telescope finds source of Magellanic Stream

2013-08-09
Astronomers using NASA's Hubble Space Telescope have solved a 40-year mystery on the origin of the Magellanic Stream, a long ribbon of gas stretching nearly halfway around our Milky Way galaxy. The Large and Small Magellanic Clouds, two dwarf galaxies orbiting the Milky Way, are at the head of the gaseous stream. Since the stream's discovery by radio telescopes in the early 1970s, astronomers have wondered whether the gas comes from one or both of the satellite galaxies. New Hubble observations reveal most of the gas was stripped from the Small Magellanic Cloud about ...

NOAA reports discovery of table coral, Acropora cytherea, off O'ahu

2013-08-09
NOAA scientists report the discovery of the first known colony of table coral off of the south shore of O'ahu in Hawai'i. A report on the discovery was published last month in the Bulletin of Marine Science. Given its common name due to its flat-topped, table-like shape, table coral (Acropora cytherea) is one of the primary reef-building corals throughout most of the tropical Pacific, but it has never been observed in waters off O'ahu - until now, researchers said. The coral, estimated to be 14 years old, was found at a depth of 60 feet during a training dive. "This ...

With early, obvious benefit of a targeted cancer drug, should expensive clinical testing continue?

2013-08-09
Generally, FDA-approved clinical trials progress through three phases: the first shows safety, the second starts to explore effects and the third seeks to prove a drug's superiority over existing treatments. But when a drug's benefit is obvious in the first or second phase, is the third, costly phase needed? The question is posed in a recent edition of the journal Nature Reviews: Clinical Oncology by Robert C. Doebele, MD, PhD, investigator at the University of Colorado Cancer Center and assistant professor of medical oncology at the CU School of Medicine. Doebele points ...

Poised for discovery: Gemini's much-anticipated infrared instrument goes on-sky

2013-08-09
Gemini Observatory's latest instrument, a powerful infrared camera and spectrograph at Gemini South, reveals its potential in a series of striking on-sky commissioning images released today. Gemini Observatory's latest tool for astronomers, a second-generation infrared instrument called FLAMINGOS-2, has "traveled a long road" to begin science observations for the Gemini scientific community. Recent images taken by FLAMINGOS-2 during its last commissioning phase dramatically illustrate that the instrument was worth the wait for astronomers around the world who are anxious ...

Faith-based re-entry program for prisoners saves money, reduces recidivism, Baylor study finds

2013-08-09
A faith-based prisoner re-entry program in Minnesota has saved an estimated $3 million by reducing recidivism, according to a Baylor University study published in the International Journal of Criminology and Sociology. The study is a cost-benefit analysis of the InnerChange Freedom Initiative, a program which relies heavily on volunteers and is privately funded, said study co-author Byron Johnson, Ph.D., co-director of Baylor's Institute for Studies of Religion (ISR). "The InnerChange program is a boon to taxpayers. It doesn't rely on public funding. Yet, at the same ...

Moffitt researchers identify gene variations that may help predict cancer treatment response

2013-08-09
Researchers at the Moffitt Cancer Center have identified four inherited genetic variants in non-small cell lung cancer patients that can help predict survival and treatment response. Their findings could help lead to more personalized treatment options and improved outcomes for patients. The researchers analyzed DNA sequence variations in 651 non-small cell lung cancer patients, paying close attention to 53 inflammation-related genes. They found that four of the top 15 variants associated with survival were located on one specific gene (TNFRSF10B). In the study, these ...

Rescuing neuroscience from its data deluge

2013-08-08
Before the digital age, neuroscientists got their information in the library like the rest of us. But the field's explosion has created nearly 2 million papers -- more data than any researcher can read and absorb in a lifetime. That's why a UCLA team has invented research maps. Equipped with an online app, the maps help neuroscientists quickly scan what is already known and plan their next study. The Aug. 8 edition of Neuron describes the findings. "Information overload is the elephant in the room that most neuroscientists pretend to ignore," explained principal ...

Novel and alternative sources for cell replacement treatment of retinopathy

2013-08-08
Damage or loss of photoreceptor cells is one of main culprits of visual impairment in many retinal degenerative diseases. Pharmacological treatment and surgical intervention are traditionally used to treat these retinal diseases, but they are not curative. It has been increasingly recognized that Wharton's jelly mesenchymal stem cells may differentiate into several cell lineages from all three germ layers. However, the capacity of Wharton's jelly mesenchymal stem cells to differentiate into retinal progenitor cells remains undetermined. A new study reported in the Neural ...

LAST 30 PRESS RELEASES:

Scientists model 'true prevalence' of COVID-19 throughout pandemic

New breakthrough to help immune systems in the fight against cancer

Through the thin-film glass, researchers spot a new liquid phase

Administering opioids to pregnant mice alters behavior and gene expression in offspring

Brain's 'memory center' needed to recognize image sequences but not single sights

Safety of second dose of mRNA COVID-19 vaccines after first-dose allergic reactions

Changes in disparities in access to care, health after Medicare eligibility

Use of high-risk medications among lonely older adults

65+ and lonely? Don't talk to your doctor about another prescription

Exosome formulation developed to deliver antibodies for choroidal neovascularization therapy

Second COVID-19 mRNA vaccine dose found safe following allergic reactions to first dose

Plant root-associated bacteria preferentially colonize their native host-plant roots

Rare inherited variants in previously unsuspected genes may confer significant risk for autism

International experts call for a unified public health response to NAFLD and NASH epidemic

International collaboration of scientists rewrite the rulebook of flowering plant genetics

Improving air quality reduces dementia risk, multiple studies suggest

Misplaced trust: When trust in science fosters pseudoscience

Two types of blood pressure meds prevent heart events equally, but side effects differ

New statement provides path to include ethnicity, ancestry, race in genomic research

Among effective antihypertensive drugs, less popular choice is slightly safer

Juicy past of favorite Okinawan fruit revealed

Anticipate a resurgence of respiratory viruses in young children

Anxiety, depression, burnout rising as college students prepare to return to campus

Goal-setting and positive parent-child relationships reduce risk of youth vaping

New research identifies cancer types with little survival improvements in adolescents and young adul

Oncotarget: Replication-stress sensitivity in breast cancer cells

Oncotarget: TERT and its binding protein: overexpression of GABPA/B in gliomas

Development of a novel technology to check body temperature with smartphone camera

The mechanics of puncture finally explained

Extreme heat, dry summers main cause of tree death in Colorado's subalpine forests

[Press-News.org] Scripps Research Institute study shows microRNAs can trigger lymphomas