Gewählte Publikation:
Trenk, C.
Role of miR-3150b-3p and miR-4521 in breast carcinogenesis.
[ Diplomarbeit/Master Thesis (UNI) ] TU Graz; 2020.
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Pichler Martin
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- Abstract:
- MicroRNAs are small non-coding RNAs that are known to be key regulators in basic biological processes not only in normal cells but especially in cancerous cells. Additionally, particularly miR-4521 has been found to be upregulated whereas miR-3150b-3p seemed to be downregulated in patients’ breast cancer tissues compared to normal breast tissues. However, their role in the initiation and progression in cancer is not known yet. Therefore, the aim of this study was to characterize and elucidate the functions of these microRNAs in triple negative breast cancer.
For this, the triple negative breast cancer cell lines BT-549, MDA-MB-231 and SUM159 were used for all experiments. I firstly transiently transfected these cell lines with miR-4521 and miR-3150b-3p mimics and inhibitors. In the next steps, I analyzed if there is an effect on different hallmarks of cancer with a special focus on proliferation and angiogenesis. After showing that a significant up- and downregulation of miR-4521 and miR-3150b-3p can be achieved in my experimental model system, I found that the mimic led to an increase in proliferation, whereas the inhibitor demonstrated the opposite effect. These results were confirmed in a colony formation unit assay where the inhibitor led to the formation of significantly less colonies while the mimics showed an increase. In the case of miR-3150b-3p also the inhibitor resulted in a slight increase in proliferation and the mimic seemed to inhibit colony formation. Moreover, it has been shown that miR-4521 overexpression led to a higher number of tubes in the tube formation assay in human endothelial cells. Again, the inhibition resulted in the opposite results.
Altogether, these data suggest that miR-4521 plays an important role in cellular growth as well as angiogenesis and might act as tumour suppressor in triple negative breast cancer. Contrary, the role of miR-3150b-3p needs to be further investigated as the results are contradictory.