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 3,500+ scientific posters on ePosters
  • More than 5,000+ 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
Scientists Find Lethal Vulnerability in Treatment-Resistant Lung Cancer
The study describes how the drug Selinexor killed lung cancer cells and shrank tumors in mice when used against cancers driven by the aggressive and difficult-to-treat KRAS cancer gene.
‘Cellbots’ Chase Down Cancer, Deliver Drugs Directly to Tumors
Programmable T cells shown to be versatile, precise, and powerful in lab studies.
Nanosensors Could Determine Tumours’ Ability to Remodel Tissue
Researchers design nanosensors that can profile tumours, focusing on protease levels.
Developing Novel Ear Infection Treatments
Research team engineers antibiotic gel for treating middle ear infections.
Blood Pressure Drug May Boost Effectiveness of Lung Cancer Treatment
Researchers at Imperial College London have suggested that the blood pressure drug may make a type of lung cancer treatment more effective.
Wearable Microscope Can Measure Fluorescent Dyes Through Skin
UCLA research could make monitoring disease biomarkers easier and more cost-effective.
Potential of New Insect Control Traits in Agriculture
Researchers have discovered a protein that shows promise as an alternate corn rootworm control mechanism.
Fighting Cancer with Sticky Nanoparticles
Treatment that uses bioadhesive nanoparticles drug carriers proved more effective than conventional treatments for certain cancers.
Fighting Plant Pathogens with RNA
Researchers develop strategy that could lead to environmentally friendly fungicide to fight pathogens.
Smart Material Hunts Cancers
Team has created smart material that locates and images cancer or tumour sites in tissue.
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
3,500+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
5,000+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!