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Markers of gene, protein, or micro-RNA activity predict outcome in prostate and colorectal cancers

athways. Because of this ability to regulate gene expression, miRNAs are believed to play an important role in cancer development, and could serve as targets for novel anti-cancer drugs.

To discover which miRNAs are expressed in colon cancer, compared to normal colon tissue, researchers at Thomas Jefferson University used a microarray chip containing probes for most of the known miRNAs in human and mouse. The investigative team, led by Bruce Boman, M.D., Ph.D., director of Genetic and Preventive Medicine at Jefferson, used the array to first characterize the miRNA expression pattern in intestinal epithelium purified from normal colon tissue.

This epithelial inner lining of the colon contains about 50 million test-tube shaped crypts that line the colon. Colon cancer arises in these crypts, and researchers believe that the cells of origin are the 10-20 immortal stem cells that reside at the bottom of each crypt. The job of these stem cells is to replenish the entire lining of the colon that turns over every five days. However, a mutation in these stem cells produces mutant daughter cells, disorganized tissue architecture, and increased proliferation of crypt cells, which leads to development of colon tumors, Boman said. Hence, they then analyzed malignant colon tissues and found that there are a number of miRNAs that were changed in expression in colon cancer.

Boman, who also directs the G.I. Cancer Program at Jefferson's Kimmel Cancer Center, next purified and microdissected colonic crypts, and compared miRNA expression between the bottom tenth of the crypt, where the stem cells reside, and the upper 9/10s of the crypt. The difference in miRNA signatures between these two crypt regions, they reasoned, would distinguish stem cell from non-stem cell activity. They found a distinct signature of 16 miRNAs that characterizes the crypt bottom. Further analysis revealed that the expression pattern of these 16 miRNAs accurately predicted which colon
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Source:American Association for Cancer Research


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