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NCI Researchers Identify Colon Cancer miRNAs

NEW YORK (GenomeWeb News) – National Cancer Institute researchers have identified a handful of microRNAs associated with colon cancer progression, the US Department of Health and Human Services announced last week.
Researchers at NCI, along with collaborators at Ohio State University and the University of Hong Kong, used miRNA microarrays to find colon adenocarcinoma-related miRNAs. They found five overexpressed miRNAs and focused on one — miR-21 — whose expression increased with tumor progression. Their findings, which they believe are a first step towards using miRNAs as a colon cancer therapeutic or a diagnostic tool, were published in the Journal of the American Medical Association on January 30th.
“To the best of our knowledge, this is the largest study done so far comparing microRNA profiles and clinical outcomes in colon cancer,” senior author Curtis Harris, chief of the NCI’s Laboratory of Human Carcinogenesis, said in a statement.
Given the emerging evidence for miRNAs as regulators of a variety of processes — from gene translation and cellular proliferation to apoptosis and carcinogenesis — the researchers decided to investigate whether any of the non-coding RNA molecules were associated with colon adenocarcinoma.
Harris’ group compared miRNA profiles in colon tumors and adjacent non-cancerous tissues taken from 84 American patients recruited from Baltimore hospitals using an Ohio State miRNA microarray. They subsequently verified the results in 113 patients at a Hong Kong hospital.
Of the 37 differentially expressed miRNAs identified, 26 were expressed at higher levels in the tumors. Five were associated with poor cancer survival.
The most highly expressed — miR-21 — was enriched not only in adenocarcinoma, but also to a lesser extent in tumor precursor adenoma tissues. Because its expression correlated with the tumor stage, the researchers suggest it may be particularly promising as a therapeutic target or a biomarker for disease progression. Interestingly, in a subset of patients receiving adjuvant chemotherapy, the patients with the highest miR-21 expression also showed the poorest response to the therapy.
“We found systematic difference in microRNA expression patterns between colon tumors and paired nontumorous tissue,” the authors wrote. “Tumors with high expression of miR-21 was associated with poor survival outcome and poor response to adjuvant chemotherapy.”
While additional research is necessary to verify the results, the researchers are hopeful that a better understanding of miRNA function in colon cancer could lead to better treatments or diagnoses in the future.
“These data build both a rationale for using expression of these five microRNAs as a prognostic tool in colon cancer and lend weight to a role for miR-21 in colon cancer development and treatment,” Harris said.

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