Corporate Banner
Satellite Banner
Genomics
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

RNA Shown to Silence Cancer Suppressor Gene

Published: Tuesday, January 15, 2008
Last Updated: Tuesday, January 15, 2008
Bookmark and Share
Discovery sheds light on epigenetic mechanisms in tumor development in plants and animals.

One way cancer arises is when tumor suppressor genes that normally keep cell growth in check are mysteriously turned off. Now, researchers at Johns Hopkins have discovered that at least one tumor suppressor gene is in fact turned off by a “noncoding” single stranded RNA nucleic acid similar to its double-stranded DNA cousin.

The so-called antisense RNA is made by a gene on a neighboring strand of DNA. Most genes in the human genome have associated with them nearby antisense RNAs, which, as their name implies, are complementary to the amino acid sequences in a “sense” RNA to which they may bind and switch off.

Reporting on the discovery in the Jan. 10 issue of Nature, the Johns Hopkins team says an absolute key to fighting cancer is to figure out why and how tumor suppressor genes get silenced and identifying means of switching them back on chemically.

“This is the first time we’ve seen an antisense RNA silencing a tumor suppressor through the means of epigenetic changes,” says Hengmi Cui, Ph.D., assistant professor of molecular medicine at Hopkins.  Epigenetic changes refer to heritable changes in genetic material that are not changes in the sequence of the DNA; these could include the addition of chemical tags onto DNA or otherwise altering how compressed the DNA is in a cell.

The Johns Hopkins team notes that a similar phenomenon occurs in plants but until now has not been seen in any type of animal, including humans. “We’re really excited to see if this is a general mechanism for all tumor suppressor genes,” says Cui.

Andrew Feinberg, M.D., M.P.H., professor of medicine, oncology and molecular biology and genetics and director of the Epigenetics Center at Hopkins, says the results of the team’s experiments “bring us closer to solving two outstanding mysteries in biology, namely what all those noncoding RNAs do in cells and how tumor suppressor genes get turned off.” It turns out, he adds “that many of those noncoding RNAs may be silencing tumor suppressor genes.”

Following clues that suggested such a role for antisense RNA, the researchers first surveyed computer databases for tumor suppressor genes with known neighboring antisense RNAs. They found antisense counterparts to 21 well-known tumor suppressor genes and decided to further study one of them, p15. That gene is deleted or silenced in several types of human cancer, including melanomas, gliomas, lung and bladder carcinomas and up to 60 percent of leukemias.

The research team first analyzed leukemia cells for the presence of antisense p15. Of 16 patient samples, 11 showed an increase in antisense p15 and decreased p15. The researchers confirmed in other experiments that the more antisense p15 a cell contained the less sense p15 it was likely to have, strong evidence that the antisense was somehow turning down the normal, sense version.

Chemically turning on the antisense gene, the team found, turned off the sense p15 gene. When they looked at the DNA around the p15 gene in cells, they found that the DNA was more compact and tightly packaged, which generally shuts off genes.

“Somehow, the presence of the antisense RNA leads to the formation of this tightening of the chromosome to make heterochromatin around the p15 gene, turning it off,” says Feinberg. “We’re now looking at other tumor suppressor genes to figure out how this happens and how general this phenomenon is.”

Further characterization of the antisense RNAs, according to Feinberg, could lead to their use as markers for certain types of cancer as well as targets for cancer-specific drugs and therapies.

“This initial laboratory study gives us some excellent clues of how to proceed with possible clinical studies to determine whether antisense RNAs could be used to guide therapy,” says David Gius, M.D., Ph.D., of the National Cancer Institute’s Radiation Oncology branch.


Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,400+ scientific posters on ePosters
  • More than 3,700+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Tumor-Only Genetic Sequencing May Misguide Cancer Treatment in Nearly Half of All Patients
Johns Hopkins scientists say the genetic code of tumors must be compared to patients’ noncancer genome to get a true picture.
Thursday, April 16, 2015
New Genetic and Epigenetic Contributors to Diabetes Identified
Comparison of fat cells in mice and men hints at how genes and environment conspire to produce disease.
Wednesday, January 07, 2015
When DNA Gets Sent to Time-Out
New details revealed in the coordinated regulation of large stretches of DNA.
Tuesday, January 06, 2015
CRISPR Shows Promise in Engineering Human Stem Cells
Johns Hopkins study could advance use of stem cells for treatment and disease research.
Monday, January 05, 2015
Up-close Look at Cancer on the Move
Microscopic view of metastasis could give insight about how to keep cancer in check.
Friday, November 07, 2014
Potential New 'Twist' in Breast Cancer Detection
Mouse studies reveal new and better picture of stem cells that may fuel some breast cancers.
Monday, December 07, 2009
Johns Hopkins Researchers Develop Human Stem Cell Line Containing Sickle Cell Anemia Mutation
Researchers establish a human cell-based system for studying the disease by reprogramming somatic cells to an embryonic stem cell like state.
Tuesday, June 03, 2008
Johns Hopkins Researcher Leads International Effort to Create “Proteinpedia”
A Johns Hopkins researcher has led the effort to compile to date the largest free resource of experimental information about human proteins.
Thursday, February 07, 2008
Cellular Pump Sabotages Cancer Drug Studies that use Glow Chemical
Scientists discover that a widely used means of illuminating cancer cells could undermine studies of the potential value of experimental anti-cancer drugs.
Thursday, January 03, 2008
More Functional DNA in Genome than Previously Thought
Hopkins researchers report that non-coding DNA, that contributes to inherited diseases like Parkinson’s or mental disorders, may be more abundant than we realize.
Thursday, December 20, 2007
Omicia and Johns Hopkins Receive Small Business Technology Transfer Grant from NIH
Omicia recieves a $187,700 grant from NIH to support a collaboration with Johns Hopkins University to identify genetic causes of cardiovascular disease.
Friday, August 17, 2007
Key to Lung Cancer Chemo Resistance Revealed
Products made by a gene called NRF2 normally protect cells from environmental pollutants.
Tuesday, October 17, 2006
Scientific News
Long Telomeres Associated with Increased Lung Cancer Risk
Genetic predisposition for long telomeres predicts increased lung adenocarcinoma risk.
Expanding the Brain
A team of researchers has identified more than 40 new “imprinted” genes, in which either the maternal or paternal copy of a gene is expressed while the other is silenced.
Identifying a Key Growth Factor in Cell Proliferation
Researchers discover that aspartate is a limiter of cell proliferation.
Study Uncovers Target for Preventing Huntington’s Disease
Scientists from Cardiff University believe that a treatment to prevent or delay the symptoms of Huntington’s disease could now be much closer, following a major breakthrough.
The Genetic Roots of Adolescent Scoliosis
Scientists at the RIKEN Center for Integrative Medical Sciences in collaboration with Keio University in Japan have discovered a gene that is linked to susceptibility of Scoliosis.
A Gene-Sequence Swap Using CRISPR to Cure Haemophilia
For the first time chromosomal defects responsible for hemophilia have been corrected in patient-specific iPSCs using CRISPR-Cas9 nucleases
New Tool Uses 'Drug Spillover' to Match Cancer Patients with Treatments
Researchers have developed a new tool that improves the ability to match drugs to disease: the Kinase Addiction Ranker (KAR) predicts what genetics are truly driving the cancer in any population of cells and chooses the best "kinase inhibitor" to silence these dangerous genetic causes of disease.
Understanding the Molecular Origin of Epigenetic Markers
Researchers at IRB Barcelona discover the molecular mechanism that determines how epigenetic markers influence gene expression.
New Tech Enables Epigenomic Analysis with a Mere 100 Cells
A new technology that will dramatically enhance investigations of epigenomes, the machinery that turns on and off genes and a very prominent field of study in diseases such as stem cell differentiation, inflammation and cancer has been developed by researchers at Virginia Tech.
Access Denied: Leukemia Thwarted by Cutting Off Link to Environmental Support
A new study reveals a protein’s critical – and previously unknown -- role in the development and progression of acute myeloid leukemia (AML), a fast-growing and extremely difficult-to-treat blood cancer.
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,400+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,700+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FREE!