Lung cancer is the most frequent cause of tumor-related death in Europe with Non-Small Cell Lung Cancer (NSCLC) representing 75% of all lung tumors. Its molecular pathogenesis is incompletely understood and specifically the role of functional RNAs in this deadly disease remains to be uncovered. Shifting a paradigm, RNA is now recognized not only as a mediator in protein synthesis, but as important functional molecule in the cell.
The microRNA family contributes to lung cancer development, but also other classes of non-coding RNA (ncRNA) are linked to this disease. However, their precise functions in pathological as well as physiological processes remain unknown. Previously, we discovered a ncRNA that correlates with metastasis formation in NSCLC termed MALAT-1. This project aims to characterize the cellular impact, molecular function and prognostic significance of MALAT-1 and the imprinted ncRNA H19 in lung cancer. First, experiments in cell lines with altered ncRNA abundance will unravel their impact on cellular phenotypes like proliferation or migration. Second, identification of interacting proteins of the ncRNAs will elucidate the molecular networks in which these RNAs function and further experiments will analyze their molecular function.
Lastly, characterization of the expression and localization of the ncRNAs will determine their potential use as tumor markers for diagnosis or prognosis in tumor samples as well as blood-derived circulating tumor cells. In summary, this project will shed light on important molecular and cellular functions of ncRNAs in cancer and elucidate their potential as disease markers. In parallel, it allows us to broaden our research focus which would be impossible without this funding and delve into one of the most fascinating fields in RNA biology as well as establish lasting collaborations with outstanding laboratories in the USA and facilitate the integration into the research community in Europe.
Start Date: 01.07.2009 End Date: 30.06.2013 EU Contribution: 100,000 Euro Total Costs: 100,000 Euro Funding Scheme: IRG International Reintegration Grant Scientific Coordinator: Dr Sven Diederichs, s.diederichs(at)dkfz-heidelberg.de