Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Prinz, F.
Influence of miR-545/374a cluster on the cisplatin resistance of A549 cells.
[ Diplomarbeit/Master Thesis (UNI) ] University of Graz; 2018. pp.75.
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Hrzenjak Andelko
- Panzitt Katrin
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- Abstract:
- Lung cancer is one of the most common and amongst the deadliest types of cancer. Since a local resection is often not possible due to the advanced stage of lung cancer at the time of diagnosis, chemotherapy with platinum-based compounds like cisplatin is the treatment of choice in such instances. A problem which frequently arises during cisplatin treatment, is the ability of cancer cells to develop mechanisms which can abrogate the effects of cisplatin on the cells. Therefore, in order to increase the efficiency of chemotherapeutic treatment, it is essential to understand the underlying mechanisms that lead to such chemoresistances. Through their extensive contribution to the post-transcriptional regulation of gene expression, microRNAs (miRNAs) are involved in the maintenance of physiological processes within the cell. Alterations of miRNA levels, which are often found in cancer cells, are reported to result in severe phenotypic cellular changes, including the development of cisplatin resistance. Two miRNAs, whose deregulation potentially contributes to cisplatin resistance in NSCLC, are miR-545 and miR-374a. Both miRNAs were found to be downregulated in cisplatin-resistant A549 (A549-CisR) cells compared to parental, cisplatin-sensitive A549 (A549-Par) cells. Further investigations illustrated, that a downregulation of miR-374a in A549-Par cells decreased their sensitivity to cisplatin, as well as their proliferation. Since a slower progression through the cell cycle gives the cells more time to repair cisplatin-induced DNA damage, these findings seem relevant in the context of cisplatin resistance. While downregulation of miR-545 did not influence cisplatin sensitivity of A549-Par cells, it was observed to decrease their overall robustness. In A549-CisR cells, upregulation of the miR-545/374a cluster did not influence cisplatin resistance, nor proliferation or general robustness. Potential target genes of the miR-545/374a cluster were evaluated using in silico prediction tools. A negative correlation was observed between the expression levels of the miR-545/374a cluster and the respective target genes in A549-CisR cells. Upon downregulation of miR-545, predicted target genes were found to be downregulated as well, which suggests an indirect interaction of miR-545 and the potential target genes. Further extensive research is needed to fully understand the contribution of the miR-545/374a cluster to the development of cisplatin resistance in NSCLC cells.