Navigation Links
Loss of MicroRNA decoy might contribute to development of soft-tissue sarcoma
Date:8/7/2013

COLUMBUS, Ohio 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.


'/>"/>

Contact: Darrell E. Ward
Darrell.Ward@osumc.edu
614-293-3737
Ohio State University Wexner Medical Center
Source:Eurekalert

Related medicine news :

1. New papers identify a microRNA that drives both cancer onset and metastasis
2. Moffitt Cancer Center researchers say 1 specific microrna promotes tumor growth and cancer spread
3. Atherosclerosis: Specific microRNAs promote inflammation
4. MicroRNA molecule may serve as biomarker, target for brain metastases in breast cancer patients
5. Hepatitis B virus promotes oncogenesis through microRNA modulation
6. MicroRNAs can convert normal cells into cancer promoters
7. Pint-size microRNAs show promise against weighty problem, researchers say
8. A microRNA prognostic marker identified in acute leukemia
9. Extended primary care office hours might help keep kids out of the emergency department
10. Moderate-intensity walking timed just right might help protect against Type 2 diabetes
11. Gene-Based Blood Test Might Help Spot Colon Cancer
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/27/2016)... Brooklyn, NY (PRWEB) , ... June 27, 2016 ... ... is using cutting edge technology to revolutionize the emergency ambulance transport experience for ... Many are aware of how Uber has disrupted the taxi industry through the ...
(Date:6/26/2016)... ... June 27, 2016 , ... Quality metrics are proliferating ... many ways they remain in the eye of the beholder, according to experts who ... of The American Journal of Managed Care. For the full issue, click here ...
(Date:6/26/2016)... Viejo, California (PRWEB) , ... June 26, 2016 , ... ... Final Cut Pro X. , "Film editors can give their videos a whole new ... said Christina Austin - CEO of Pixel Film Studios. , ProSlice Levels contains ...
(Date:6/26/2016)... ... ... a legally blind and certified personal trainer is helping to develop a weight loss fitness ... to fix the two major problems leading the fitness industry today:, , ... They don’t eliminate all the reasons people quit their exercise program ...
(Date:6/25/2016)... ... June 25, 2016 , ... ... and applications at AcademyHealth’s Annual Research Meeting June 26-28, 2016, at the Hynes ... important health care topics including advance care planning, healthcare costs and patient and ...
Breaking Medicine News(10 mins):
(Date:6/26/2016)... , June 27, 2016  VMS Rehab Systems, ... Board will take whatever measures required to build a ... stock which is currently listed on the OTC Markets-pink ... Company Chairman and CEO, "We are seeing an anomaly ... to understand, not only by the Company, but shareholders ...
(Date:6/24/2016)... N.J. , June 24, 2016  Collagen ... the design, development and manufacturing of collagen and ... regeneration announced today that Bill Messer ... and Marketing to further leverage the growing portfolio ... medical devices. Bill joins the Collagen ...
(Date:6/24/2016)... DUBLIN , June 24, 2016 ... and Markets has announced the addition of the ... their offering. ... products and provides an updated review, including its applications ... covering the total market, which includes three main industries: ...
Breaking Medicine Technology: