MicroRNA undermines tumor suppression

March 17, 2009 by Nicole Giese

A small piece of RNA, or microRNA (miRNA), ratchets down the activity of the tumor-suppressor gene p53, according to a study by Whitehead Institute and National University of Singapore researchers.

While p53 functions to suppress tumor formation, the is thought to malfunction in more than 50% of cancerous tumors.

The study published online March 17 in and Development reports the first time that a miRNA has been shown to directly affect the p53 gene, although researchers have previously identified other genes and miRNAs that regulate p53's activity indirectly.

"For critical genes like p53, it's important that they are maintained at the right level in the cell," says Beiyan Zhou, a postdoctoral researcher in the lab of Whitehead Member Harvey Lodish and mentor to the paper's first author, Minh Le. "Le's work describes one more layer of regulatory mechanism that balances p53 gene expression."

miRNAs, short snippets of RNA, usually reduce how often a certain gene is translated into a protein. When a miRNA matches with and binds to a given coding for a specific protein, thereby preventing that messenger RNA from acting as a template for protein creation.

To investigate whether any miRNAs directly affect p53, Le, who is a joint graduate student in Lodish's lab and in the lab of Bing Lim at the National University of Singapore, searched the p53 gene for any sites that matched with known miRNAs from two databases. Only miRNA125b potentially has p53 target sites in humans, in zebrafish, and in many other vertebrates, indicating that it was important enough in cellular processes to be conserved through evolution.

Le tested miRNA125b's effects on several types of known to express p53, including human neural and lung cells. When Le reduced the amount of miRNA125b in the cells, p53 levels and the number of cells undergoing apoptosis (a type of that can be triggered by p53) both increased, whereas an increase in miRNA125b levels decreased levels of p53 and the number of apoptotic cells.

To confirm that miRNA125b played a similar role in developing organisms, Le changed the miRNA125b levels in zebrafish embryos. When she reduced miRNA125b levels in the embryos, cellular p53 levels and apoptosis both increased.

"Taking all of this data together, the p53 pathway is a major target of miRNA125b," says Lodish, who is also a professor of biology and bioengineering at MIT. "Most miRNAs have multiple targets, but there are a few cases that a miRNA has one major target and this is one of them."

More information: "MicroRNA-125b is a novel negative regulator of p53" Genes & Development, online March 18, 2009

Source: Whitehead Institute for Biomedical Research (news : web)

Explore further: Preventing cancer without killing cells

Related Stories

Preventing cancer without killing cells

March 30, 2007

Inducing senescence in aged cells may be sufficient to guard against spontaneous cancer development, according to a paper published online this week in EMBO reports. It was previously unknown whether cellular senescence or ...

Common cancer gene sends death order to tiny killer

May 31, 2007

Scientists at Johns Hopkins have discovered one way the p53 gene does what it's known for—stopping the colon cancer cells. Their report will be published in the June 8 issue of Molecular Cell.

Newly discovered gene plays vital role in cancer

February 27, 2009

(PhysOrg.com) -- Gene p53 protects against cancer and is usually described as the most important gene in cancer research. However, scientists at the Swedish medical university Karolinska Institutet have now shown that a previously ...

Recommended for you

Most EU nations seek to bar GM crops

October 4, 2015

Nineteen of the 28 EU member states have applied to keep genetically modified crops out of all or part of their territory, the bloc's executive arm said Sunday, the deadline for opting out of new European legislation on GM ...

Trade in invasive plants is blossoming

October 3, 2015

Every day, hundreds of different plant species—many of them listed as invasive—are traded online worldwide on auction platforms. This exacerbates the problem of uncontrollable biological invasions.

Ancestral background can be determined by fingerprints

September 28, 2015

A proof-of-concept study finds that it is possible to identify an individual's ancestral background based on his or her fingerprint characteristics – a discovery with significant applications for law enforcement and anthropological ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.