Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Kapeller, A.
Evaluation of the therapeutic potential of the lncRNA NORAD in combination with PARP inhibitors in triple negative breast cancer.
[ Diplomarbeit/Master Thesis (UNI) ] TU Graz; 2021. pp.62.
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Pichler Martin
- Altmetrics:
- Abstract:
- Non-coding RNAs has been initially recognized as molecular fossils of the RNA world. During the last decade this perception has been changed since it became evident that they play important roles in various cellular processes, in particular gene regulation. More prominently, non-coding RNAs have demonstrated to be central in the pathogenesis of certain diseases such as Prader-Willi syndrome or even cancer. One of them, a long non-coding RNA activated by DNA damage (NORAD) was reported to play a role in maintaining genomic integrity by negatively regulating proteins that degrade mRNAs for proteins which are important for DNA repair. PARP inhibitors (PARPi) are a type of drugs that inhibit the action of poly(ADP-ribose)-polymerases, which are important for the detection and repair of DNA-damage. These drugs are frequently used in patients with mutations in other DNA repair proteins such as BRCA1 or BRCA2. As a result, these cells are unable to effectively repair DNA damage and are sensitized to DNA damaging agents such as chemotherapeutics. Therefore, we hypothesized, that a knockdown of NORAD in combination with PARPi might lead to a defect in DNA repair and increased cell death. We found the expression of NORAD is upregulated in various triple negative breast cancer cell lines and a knockdown of this lncRNA led to reduced proliferation in those cell lines. These results imply a mechanistic relationship between NORAD expression and TNBC. However, in this study, no evidence was found that NORAD knockdown cells were impaired in DNA repair and reduced NORAD levels did not increase cell sensitivity to DNA damaging agents cisplatin or olaparib.