MicroRNA (miRNA) has a significant role in controlling developmental and cancer processes like cell proliferation, differentiation, cell cycle, apoptosis, and metastasis. This ubiquitousness and their recently revealed role as key regulators of gene expression during development has boosted their use as agents in the fight against cancer. It’s a hot topic “and it’s getting hotter,” said Frank Slack, associate professor of molecular, cellular, and developmental biology at Yale University, at the Keystone Symposium “MicroRNA and Cancer” held earlier this year.
According to Curtis Harris, M.D., chief, laboratory of human carcinogenesis at the NIH, “throughout the community, there is a lot of interest in translational science, which you can see from the number of papers published in the last few years.”
It’s generally accepted that alterations in the expression of miRNA genes contribute to the pathogenesis of most, possibly all, human malignancies. “We found that these alterations can be caused by various mechanisms, including deletions, amplifications, or mutations involving miRNA loci, epigenetic silencing, or the dysregulation of transcription factors that target specific miRNAs,” noted Carlo Croce, M.D., director of human cancer genetics at the Ohio State University Comprehensive Cancer Center.
“Because malignant cells show dependence on the dysregulated expression of miRNA genes, which in turn control or are controlled by the dysregulation of multiple protein-coding oncogenes or tumor suppressor genes, these small RNAs provide important opportunities for the development of future miRNA-based therapies.”
At the meeting, Dr. Croce presented some of his group’s discoveries on the role that miR-21 plays in the EGF receptor pathway in cancer. “It’s an interesting issue; there is either loss of expression or overexpression of miRNAs in cancer. We found in particular that miR-21 is dysregulated in six out of six solid tumors.
“We have found dysregulation of miR-21 in 13 out of 13 different types of malignancies. By microarray and RT-PCR, we now know that miRNAs are dysregulated by pathways that are involved in cancer. The fact that miRNAs are downstream targets of pathways involving cancer provides tremendous opportunity for therapy. Many components of the pathway causing cancer may be undruggable. On the contrary, miRNAs that are downstream targets are druggable.”
Dr. Croce showed that the global expression of miRNA indicated specific signatures for every human cancer. “We did a systematic study and discovered how each miRNA is dysregulated, and discovered signatures for early and late stages of human cancer. In the future, we’ll use this information to develop miRNA therapies.”