Role Of MicroRNA Identified In Thyroid Cancer

http://www.sciencedaily.com/releases/2005/12/051223085503.htm

Source: Ohio State University Medical Center
Date: 2005-12-23

Role Of MicroRNA Identified In Thyroid Cancer

The presence of only five tiny strands of RNA is enough to clearly
distinguish cancerous thyroid tissue from otherwise normal tissue,
scientists say.

The findings provide more evidence that an emerging set of RNA genes
called microRNA (miRNA) is a powerful regulatory force in the development
of cancer and other diseases. The study is published online in the Dec. 19
Proceedings of the National Academy of Sciences.

Scientists already know that some people inherit a predisposition to
developing papillary thyroid cancer (PTC), the most common form of thyroid
cancer, representing about 80 percent of all cases. Although changes in
key cell-signaling systems and gene translocations are sometimes present
in thyroid tumors, no specific gene mutations have yet been identified
that are directly linked to the predisposition of this type of cancer.

That led researchers in The Ohio State University Comprehensive Cancer
Center to conclude that while genetic mutations may indeed cause some
people to be more likely to develop PTC than others, the mutations may not
occur often enough to be readily detectable. They hypothesized that any
predisposition to PTC might be more reasonably linked to a more subtle,
complex interaction among several genes ? suggesting a possible role for
miRNAs.

MiRNAs are smidgens of genetic material no longer than 22 or so
nucleotides in length. A gene, in comparison, can be tens of thousands of
nucleotides long. Scientists used to think miRNAs were parts of long
stretches of functionless, ?junk? DNA in the genome. But Dr. Huiling He, a
research scientist in the Human Cancer Genetics Program at Ohio State and
the lead author of the study, says researchers are now beginning to
understand how important they may be.

?The identification of miRNA ?signatures? in cancer and other diseases has
really changed the way we think about the process of malignant growth,?
says He.

Old dogma held that a gene carries a recipe for a molecule of messenger
RNA which, in turn, carries a blueprint for the creation of a particular
protein. Any mutation in the gene could affect the production of the
protein. But recent studies have shown that protein production can also be
manipulated indirectly through miRNAs.

?MiRNAs can latch on to part of the messenger RNA and scramble its ability
to properly carry out its original coding instructions,? says He.

Under the direction of Dr. Albert de la Chapelle, a professor in the
department of molecular virology, immunology and medical genetics at Ohio
State, He and other researchers examined samples of malignant tissue from
15 patients diagnosed with PTC and compared them with normal appearing
tissue adjacent to the tumors.

They found 23 miRNAs that were significantly altered in the cancerous
tissue when compared with the normal samples, with three of the miRs ?
miR-146, miR-221 and miR-222 ? dramatically overexpressed, or ?turned on,?
registering 11-to-19-fold higher levels of expression in the tumors than
in the unaffected tissue nearby.

Further investigation revealed that two additional miRs ? miR-21 and
miR-181a ? when coupled with the three that showed dramatic
overexpression, formed a ?signature? that clearly predicted the presence
of malignant tissue.

?We also discovered miR-221 expression in all of the apparently normal
tissue of the patients with PTC, but it was significantly overexpressed in
a subset of three of the samples, suggesting that increased activity of
miR-221 may be one of the earliest signs of carcinogenesis,? says de la
Chapelle.

Some scientists believe miRNAs act like oncogenes, molecules that promote
cell growth, and they also feel they may be tumor and tissue specific. For
example, in many other forms of cancer, miRNA activity is suppressed, but
in PTC, researchers found just the opposite: 17 of the 23 miRNAs they
discovered were overexpressed.

According to the American Cancer Society, the incidence of thyroid cancer
has been increasing slightly over the past several years. It estimates
that about 25,000 new cases will be diagnosed in the United States this
year.

?This is just the beginning of our work identifying the role of miRNAs in
thyroid cancer,? says He. ?But we are encouraged by these findings. We
feel that they help point the way toward new options in diagnosis and
treatment for this disease.?

A grant from the National Institutes of Health supported the research
team, which included Drs. Krystian Jazdzewski, Wei Li, Stefano Volinia,
George Calin, Carlo Croce and Chang-gong Liu, all of the Ohio State Human
Cancer Genetics Program; Dr. Saul Suster, from OSU?s department of
pathology; Dr. Richard Kloos from OSU?s departments of internal medicine
and radiology; Rebecca Nagy, a genetic counselor in the Human Cancer
Genetics Program; Sandra Liyanarachchi, a biostatistician in the Ohio
State Human Cancer Genetics Program; and Dr. Kaarle Franssila, from the
department of pathology at Helsinki University Central Hospital, Finland.

Editor's Note: The original news release can be found here.

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