PT  - JOURNAL ARTICLE
AU  - Maria Polycarpou-Schwarz
AU  - Tony Gutschner
AU  - Stefanie Grund
AU  - Arne Warth
AU  - Heike Zabeck
AU  - Catherina Hildenbrand
AU  - Marion Baas
AU  - Michael Meister
AU  - Thomas Muley
AU  - Peter Schirmacher
AU  - Hans Hoffmann
AU  - Philipp Schnabel
AU  - Sven Diederichs
TI  - Non-coding RNA as functional player and molecular marker in lung cancer
DP  - 2011 Sep 01
TA  - European Respiratory Journal
PG  - p1959
VI  - 38
IP  - Suppl 55
4099  - http://erj.ersjournals.com/content/38/Suppl_55/p1959.short
4100  - http://erj.ersjournals.com/content/38/Suppl_55/p1959.full
SO  - Eur Respir J2011 Sep 01; 38
AB  - Previous research has almost exclusively focused on protein-coding genes as functional players in cancer as well as diagnostic or prognostic molecular markers. However, it is now evident, that the human genome contains many more functionally important and clinically informative entities: the non-coding RNAs (ncRNA). To assess the expression landscape of this new class of molecules, we have profiled the expression of 17000 non-coding RNAs in comparison to 22000 protein-coding mRNAs in early stages of lung adenocarcinoma and matched non-malignant lung tissue. These studies revealed molecular signatures associated with tumorigenesis (tumor vs. normal; diagnostic value), with histological subtypes (acinar vs. solid) as well as with the outcome and metastasis development (prognostic value).Eight novel, differentially expressed transcripts named “Lung Cancer intergenic RNA” (LuCaiR1 - LuCaiR8) were validated and selected for functional characterization, for which we have implemented several technologies. To identify the molecular RNA-protein-networks in which the ncRNAs could function, we use RNA affinity purification and mass spectrometry. To study loss-of-function phenotypes in human lung cancer cells, we have developed a novel technique to create functional knockouts of ncRNAs in human lung cancer cell lines using Zinc Finger Nucleases. This strategy allows the specific and stable silencing of the targeted ncRNA without off-target effects for functional studies. Our research uncovers the functions at the cellular and molecular level of the differentially regulated ncRNAs as well as their clinical importance as diagnostic and prognostic markers.