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

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 in the Proceedings of the National Academy of Sciences ( PNAS ).

Researchers 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 papillary thyroid cancer than others, the mutations may not occur often enough to be readily detectable.
They hypothesized that any predisposition to papillary thyroid cancer 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.
Researchers used to think miRNAs were parts of long stretches of functionless, “junk” DNA in the genome. But Huiling He, 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 Albert de la Chapelle, at Ohio State, He and other researchers examined samples of malignant tissue from 15 patients diagnosed with papillary thyroid cancer 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 papillary thyroid cancer, 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 researchers 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 papillary thyroid cancer, 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.

Source: Ohio State University Medical Center, 2005


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