MedicalResearch.com Interview with:
Ahmad M. Khalil, PhD
Department of Genetics
School of Medicine
Case Western Reserve University
Cleveland, Ohio 44106-4955
Medical Research: What is the background for this study? What are the main findings?
Dr. Khalil: DNA in human cells is modified chemically by methylation. The process of DNA methylation plays important roles in protecting human DNA and ensures proper gene expression. In cancer cells, the process of DNA methylation becomes deregulated, however, the mechanisms of how this occurs are not known. In our study, we have uncovered a novel mechanism on how colon cancer cells change their DNA methylation, and consequently, become more tumorigenic. We specifically identified a long non-coding RNA that interacts with and regulates the enzyme that modifies DNA with methylation – the enzyme is called DNMT1. This lncRNA become suppressed in colon tumors, which we believe is a key step in loss of DNA methylation in colon cancer cells.
Medical Research: What should clinicians and patients take away from your report?
Dr. Khalil: Our current findings help explain the loss of DNA methylation in cancer cells and why its loss, or changes in its patterns, contribute to the development of cancer. We hope that our research will contribute toward the development of new therapies to target tumors using RNA-based therapies, an increasingly attractive modality for delivering targeted effective treatments.
Medical Research: What recommendations do you have for future research as a result of this study?
Dr. Khalil: Our genome (DNA) is very complex and much more research is needed to understand the function of novel genes that encode a new class of molecules that we refer to as long non-coding RNAs. These novel molecules have the potential to unlock many secrets of our genome. For now in the colon cancer space, we want to explore the role of other key lncRNAs among the 148 of those associated with DNMT1 in colon cells. Perhaps these other beneficial lncRNAs affect the suppression of colon cancer growth in a synergistic effect within the same pathway. There may be potential to develop methods to reactivate beneficial lncRNAs endogenously or even change gene expression of many other genes to slow colon cancer growth even more.
Callie R. Merry, Megan E. Forrest, Jessica N. Sabers, Lydia Beard, Xing-Huang Gao, Maria Hatzoglou, Mark W. Jackson, Zhenghe Wang, Sanford D. Markowitz, Ahmad M. Khalil. DNMT1-associated long non-coding RNAs regulate global gene expression and DNA methylation in colon cancer. Human Molecular Genetics, 2015; ddv343 DOI:1093/hmg/ddv343
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Ahmad M. Khalil, PhD (2015). RNA Can Promote Colon Cancer Progression