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

Loss of MicroRNA Decoy Might Contribute to Development of Soft-Tissue Sarcoma

Published: Thursday, August 08, 2013
Last Updated: Thursday, August 08, 2013
Bookmark and Share
Knowledge of this mechanism could guide the design of new, more effective treatments.

Researchers have discovered a novel mechanism responsible for the loss of a critical tumor-suppressor gene in rhabdomyosarcoma and other soft-tissue sarcomas, rare cancers that strike mainly children and often respond poorly to treatment. Their cause is largely unknown.
 
Knowledge of the mechanism could guide the development of more effective therapies for these malignancies, say researchers who led the study at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James).
 
The researchers found that the tumor-suppressor gene called A20 is silenced not by mutation, as in many other cancers, but because a second molecule is lost, a small molecule called microRNA-29 (miR-29). In addition, they found that miR-29 normally protects A20 from destruction. When miR-29 is absent, A20 is degraded. Loss of A20, in turn, leads to a dramatic rise in levels of a protein called NF-kB and to tumor progression.
 
The findings are published in the journal Science Signaling.
 
“We do know that NF-kB is a tumor promoter, but we don't know why it is upregulated in many cancers,” says principal investigator Denis Guttridge, PhD, professor of molecular virology, immunology and medical genetics and a member of the OSUCCC – James Molecular Biology and Cancer Genetics Program.
 
“Our study indicates that it involves a regulatory circuit between NF-kB, miR-29 and the A20 tumor-suppressor gene,” Guttridge says. “It also identifies NF-kB as a therapeutic target in sarcoma and A20 and miR-29 as potential biomarkers for sarcoma.”
 
“We are excited about these findings because they open up new vistas on the role of microRNAs in sarcoma development and provide a rationale for further interrogating this circuitry as a potential target for new treatments,” says study pathologist and coauthor O. Hans Iwenofu, MD, FCAP, assistant professor of pathology and member of the OSUCCC – James Molecular Biology and Cancer Genetics Program.
 
Soft-tissue sarcomas – cancers of muscle, other soft tissues and bone – make up about 15 percent of pediatric cancer cases. In 2013, about 11,400 cases of sarcoma are expected in the United States, and about 4,400 Americans are expected to die from the malignancy.
 
For this study, Guttridge, Iwenofu and their colleagues used human tumor samples, cell lines and animal models. Key technical findings include:

•    miR-29 and A20 expression are abnormally low in sarcomas;
•    The A20 gene showed little evidence of mutation;
•    Restoring miR-29 levels in sarcoma cells caused A20 levels to rise;
•    miR-29 normally binds with a protein called HuR; when miR-29 is absent, HuR binds with A20, leading to the degradation of A20;
•    When miR-29 binds with HuR, it acts as a decoy and protects A20 from HuR-mediated degradation.

“The loss of the A20 tumor-suppressor gene because the microRNA decoy is absent may represent another mechanism to explain why NF-kB is constitutively active in sarcoma cancers,” Guttridge says.
 
Funding from the NIH/National Cancer Institute (grants CA163995-01, CA143082) and a Pelotonia fellowship supported this research.


Further Information

Join For Free

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 3,000+ scientific posters on ePosters
  • More than 4,500+ 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

HPV Can Damage Genes and Chromosomes Directly, Sequencing Study Shows
This study shows that HPV can damage genes and chromosomes directly, revealing a new way by which HPV might contribute to cancer development.
Tuesday, November 12, 2013
Nano Drug Crosses Blood-Brain Tumor Barrier
This laboratory study shows that a nanotechnology drug called SapC-DOPS crosses barrier and targets brain-tumor cells and retards growth of tumor blood vessels.
Monday, July 22, 2013
Study Shows How the Nanog Protein Promotes Growth of Head and Neck Cancer
A protein called Nanog helps the renewal of healthy embryonic stem cells and promotes cancer stem cell proliferation in head and neck cancer.
Monday, June 24, 2013
Scientific News
AACR 2016: Cancer Immunotherapy and Beyond
At this year's meeting there was a palpable buzz around subjects ranging from microbiomics to the tumor microenvironment and cancer vaccines, big data to in vitro and in vivo modeling and drug delivery (to name just a few).
Turning Skin Cells into Heart, Brain Cells
In a major breakthrough, scientists at the Gladstone Institutes transformed skin cells into heart cells and brain cells using a combination of chemicals.
Detection of HPV in First-Void Urine
Similar sensitivity of HPV test on first void urine sample compared to cervical smear.
Potential “Good Fat” Biomarker
New method to measure the activity of energy consuming brown fat cells could ease the testing weight loss drugs.
Shape Of Tumor May Affect Whether Cells Can Metastasize
Illinois researchers found that the shape of a tumor may play a role in how cancer cells become primed to spread.
MicroRNA Pathway Could Lead to New Avenues for Leukemia Treatment
Cancer researchers at the University of Cincinnati have found a particular signaling route in microRNA (miR-22) that could lead to targets for acute myeloid leukemia, the most common type of fast-growing cancer of the blood and bone marrow.
Analysis of Dog Genome will Provide Insight into Human Disease
An important model in studying human disease, the non-coding RNA of the canine genome is an essential starting point for evolutionary and biomedical studies – according to a new study led by The Genome Analysis Centre (TGAC).
New Blood Test for The Earlier Diagnosis of Breast Cancer Spread
Researchers at University of Westminster have confirmed that a new blood test can detect if breast cancer has spread to other parts of the body.
First Gene Therapy Successful Against Human Aging
American woman gets biologically younger after gene therapies.
Targeting an ‘Undruggable’ Cancer Gene
RAS genes are mutated in more than 30 percent of human cancers and represent one of the most sought-after cancer targets for drug developers.
SELECTBIO

SELECTBIO Market Reports
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
3,000+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,500+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!