Medical Research: What is the background for this study? What are the main findings?
Response: The lung transcription factor Nkx2-1 is an important gene regulating lung formation, and normal respiratory functions after birth. Alteration in the expression of this transcription factor can lead to lung interstitial disease, postnatal respiratory distress and lung cancer. MicroRNAs repress gene expression, also controlling lung cell differentiation. In this study, we characterized miRNAs regulated by Nkx2-1 in lung cells by genome-wide analysis and confirm the expression patterns of highly regulated miRNAs in normal lung and in lungs lacking functional Nkx2-1. By in vitro studies in lung cell lines we found that down-regulation of Nkx2-1 de-represses miR-200c. Increased miR-200c, in turn, reduces the expression of its predicted targets Nfib and Myb. These findings add new components to the gene regulatory network controlled by Nkx2-1 in lung epithelial cells that may have implications in the various roles of Nkx2-1 in development and disease particularly in this case lung cancer where the levels are seriously altered.
Medical Research: What should clinicians and patients take away from your report?
Response: Clinicians and patients may take away the fact that these new regulatory mechanisms driven by Nkx2-1 in lung epithelial cells may have implications in the control lung cell proliferation, tumor formation and progression. Increasing the knowledge about the mechanisms of lung tumorigenesis will lead to improving diagnosis and treatment. The findings appear in the journal Respiratory Research: http://respiratory-research.com/content/16/1/22
Medical Research: What recommendations do you have for future research as a result of this study?
Response: As the regulatory mechanisms studied in this project are linked to tumor suppression our findings have the potential to contribute to the control of lung tumor formation. We are now using the results from this study to evaluate mechanisms of prevention and treatment in a lung cancer model with the hope of improving disease outcomes. We are testing a novel drug delivery system developed in our laboratory using a Nano Emulsion Technology to target-deliver miRNAs such as miR-200c into cancer cells to inhibit its predicted targets Nfib and Myb, two strong oncogenes.
MedicalResearch.com Interview with:Jean-Bosco Tagne Ph.D. (2015). New Mechanism Driving Lung Cancer Elucidated