Division of RNA Biology and Cancer
Prof. Dr. Sven Diederichs
Recent insights into RNA biology induced a paradigm shift towards the recognition of RNAs as functionally important molecules - beyond serving as messengers for protein-encoding genes. A large fraction of the human genome is transcribed into RNA (up to 70%), while only 2% are protein-encoding. Non-protein-coding RNAs execute important functions in the cell. Very short non-coding RNAs, the microRNAs, play important roles in gene regulation. The tumor-suppressive or oncogenic role of many microRNAs and their frequent deregulation in tumors allow a first glimpse of the striking role that non-coding RNAs could play in cancer. Novel long non-coding RNAs (ncRNA, lncRNA, lincRNA) fulfill important functions in epigenetic regulation, chromatin remodeling or splicing. Taken together, the human cell contains many more RNAs than previously anticipated and many of them might just await their discovery as functionally important molecules in cancer.
Our research focuses on long non-coding RNAs (lncRNAs) and their role in cancer. After profiling the expression of thousands of ncRNAs in three tumor entities (lung, liver and breast cancer), we elucidate the cellular and molecular functions of differentially regulated ncRNAs in cancer using innovative techniques like the CRISPR/Cas9 system, RNA Affinity Purification and our own customized siRNA library targeting specifically cancer-associated lncRNAs. Our RNAi screens have uncovered numerous lncRNAs controlling several hallmarks of cancer including cancer cell viability, mitosis and migration.
Winter, J.; Jung, S.; Keller, S.; Gregory, R.I.; Diederichs, S. (2009). Many roads to maturity: microRNA Biogenesis pathways and their regulation. Nat. Cell Biol., 11, 228-234
T Gutschner, M Hämmerle, M Eißmann, J Hsu, Y Kim, G Hung, AS Revenko, G Arun, M Stentrup, M Groß, M Zörnig, AR MacLeod, DL Spector, S Diederichs: "The non-coding RNA MALAT1 is a critical regulator of the metastasis phenotype of lung cancer cells" Cancer Research (2013) 73: 1180-1189
Diederichs, S. & Haber, D.A. (2007). Dual role for Argonautes in microRNA processing and posttranscriptional regulation of microRNA expression. Cell, 131, 1097-1108
Gutschner T, Baas M, Diederichs S: "Non-coding RNA gene silencing through genomic integration of RNA destabilizing elements using zinc finger nucleases" Genome Research (2011) 21: 1944-1954