Featured Research

from universities, journals, and other organizations

MicroRNA linked to shut-down of DNA-repair genes

Date:
April 30, 2010
Source:
Ohio State University Medical Center
Summary:
New research shows that microRNA can silence genes that protect against cancer-causing mutations. The study found that microRNA-155 can inhibit the activity of mismatch repair genes, which normally correct damage that occurs when the wrong bases are paired in DNA. Loss of these genes causes cancer-susceptibility syndromes and can contribute to colorectal, uterine, ovarian, and other cancers. It is the first evidence that deregulation of microRNAs can cause genomic instability, a characteristic of cancer cells.

New research shows for the first time that molecules called microRNA can silence genes that protect the genome from cancer-causing mutations.

Related Articles


The study, led by researchers at the Ohio State University Comprehensive Cancer Center-Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, shows that microRNA-155 (miR-155) can inhibit the activity of genes that normally correct the damage when the wrong bases are paired in DNA.

The loss or silencing of these genes, which are called mismatch repair genes, causes inherited cancer-susceptibility syndromes and contributes to the progression of colorectal, uterine, ovarian and other cancers.

"This is the first evidence that deregulation of microRNAs can cause genomic instability, a characteristic of cancer cells," says principal investigator Dr. Carlo M. Croce, professor of molecular virology, immunology and medical genetics, and director of Ohio State's Human Cancer Genetics program.

"We discovered that miR-155 targets and downregulates mismatch repair genes and that overexpression of miR-155 results in an increase in genomic alterations that contribute to cancer pathogenesis," he says.

The study was published recently in the Proceedings of the National Academy of Sciences and shows the following:

  • Overexpression of miR-155 reduced the expression of the human mismatch repair genes MLH1, MSH2 and MSH6 by 72 percent, 42 percent and 69 percent, respectively, in a colorectal cancer cell line.
  • High expression of miR-155 in human colorectal tumors correlates with low expression of MLH1 and MSH2.
  • Human tumors that feature unexplained mismatch repair inactivation showed miR-155 overexpression.

The third finding may explain a colon-cancer conundrum. About five percent of colorectal cancer cases feature a genomic marker called microsatellite instability that signals the loss of mismatch repair ability and the presence of an inherited cancer predisposition condition. These cases also show no expression of mismatch genes. Yet, the genes themselves show no alterations that explain the loss of expression.

"This study describes a totally new mechanism that might explain those cases of colorectal cancer that display microsatellite instability but no mutations or epigenetic inactivation of the mismatch repair genes," says co-author Muller Fabbri, a research scientist with the OSUCCC-James.

Overall, Croce says, "Our findings suggest that miR-155 expression might be an important stratification factor in the prognosis and treatment of cancer patients and provide an additional analytical test for exploring the etiology of microsatellite-instability tumors when the standard tests do not provide a conclusive diagnosis."

Funding from the National Cancer Institute, National Institute of General Medical Sciences and Associazione Italiana Ricerca sul Cancro supported this research.

Other Ohio State researchers involved in this study were Nicola Valeri, Pierluigi Gasparini, Chiara Braconi, Angelo Veronese, Francesca Lovat, Brett Adair, Arianna Bottoni, Stefan Costinean, Sukhinder K. Sandhu, Gerard J Nuovo, Hansjuerg Alder, Federica Calore, Stefano Volinia, Michael A. McIlhatton and Richard Fishel.


Story Source:

The above story is based on materials provided by Ohio State University Medical Center. Note: Materials may be edited for content and length.


Journal Reference:

  1. N. Valeri, P. Gasparini, M. Fabbri, C. Braconi, A. Veronese, F. Lovat, B. Adair, I. Vannini, F. Fanini, A. Bottoni, S. Costinean, S. K. Sandhu, G. J. Nuovo, H. Alder, R. Gafa, F. Calore, M. Ferracin, G. Lanza, S. Volinia, M. Negrini, M. A. McIlhatton, D. Amadori, R. Fishel, C. M. Croce. Modulation of mismatch repair and genomic stability by miR-155. Proceedings of the National Academy of Sciences, 2010; 107 (15): 6982 DOI: 10.1073/pnas.1002472107

Cite This Page:

Ohio State University Medical Center. "MicroRNA linked to shut-down of DNA-repair genes." ScienceDaily. ScienceDaily, 30 April 2010. <www.sciencedaily.com/releases/2010/04/100430091603.htm>.
Ohio State University Medical Center. (2010, April 30). MicroRNA linked to shut-down of DNA-repair genes. ScienceDaily. Retrieved November 22, 2014 from www.sciencedaily.com/releases/2010/04/100430091603.htm
Ohio State University Medical Center. "MicroRNA linked to shut-down of DNA-repair genes." ScienceDaily. www.sciencedaily.com/releases/2010/04/100430091603.htm (accessed November 22, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Saturday, November 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

WFP: Ebola Risks Heightened Among Women Throughout Africa

WFP: Ebola Risks Heightened Among Women Throughout Africa

AFP (Nov. 21, 2014) Having children has always been a frightening prospect in Sierra Leone, the world's most dangerous place to give birth, but Ebola has presented an alarming new threat for expectant mothers. Duration: 00:37 Video provided by AFP
Powered by NewsLook.com
Could Your Genes Be The Reason You're Single?

Could Your Genes Be The Reason You're Single?

Newsy (Nov. 21, 2014) Researchers in Beijing discovered a gene called 5-HTA1, and carriers are reportedly 20 percent more likely to be single. Video provided by Newsy
Powered by NewsLook.com
Raw: Paralyzed Marine Walks With Robotic Braces

Raw: Paralyzed Marine Walks With Robotic Braces

AP (Nov. 21, 2014) Marine Corps officials say a special operations officer left paralyzed by a sniper's bullet in Afghanistan walked using robotic leg braces in a ceremony to award him a Bronze Star. (Nov. 21) Video provided by AP
Powered by NewsLook.com
Milestone Birthdays Can Bring Existential Crisis, Study Says

Milestone Birthdays Can Bring Existential Crisis, Study Says

Newsy (Nov. 21, 2014) Researchers find that as people approach new decades in their lives they make bigger life decisions. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins