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Common molecular 'signature' identified in solid tumors

nia and George Calin found 137 different miRNAs expressed in at least half of the cancers, with 43 miRNAs allowing scientists to distinguish the difference between normal and malignant tissue.

Further tests showed that 21 of the distinguishing miRNAs were deregulated in at least three of the cancers ?and in some cases, as many as five or all six. The researchers defined this limited set as the "miRNA signature" in solid tumors.

Croce says finding such a signature is important because it shows that many forms of cancer share common genetic pathways that become scrambled as cancer takes hold and spreads. He says narrowing the list of the most active ones provides a guide to directing future research.

"We know that there are hundreds of miRNAs, and some of them may have multiple gene targets. Finding the ones that appear over and over again in various forms of cancer will help us design new and better interventions," says Croce.

MiRNAs can behave like oncogenes, which promote tumor growth, or tumor suppressors, which keep potentially malignant cells in check. Croce points out that miRNA activity is tissue-sensitive, meaning some miRNAs may be overexpressed, or "turned on" in some of the cancers while in others they are underexpressed, or "turned off."

In the six types of cancer in the study, the majority (26) of the miRNAs were overexpressed, while 17 were underexpressed.

Calin and Volinia also identified several key cancer genes the miRNA signature targets, including the tumor suppressors retinoblastoma-1 (RB1) and transforming growth factor, beta receptor 2 (TGFBR2).

Croce predicts that miRNAs themselves may one day be used as treatments. "If we can replace miRNAs that are lost and block those that are overly abundant, then maybe we can prevent some of the very earliest changes that happen in the development of cancer. There is a lot of work that still needs to be done, but I am convinced that this field
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Source:Ohio State University


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