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The Influence of Salinomycin on the Expression Profile of mRNAs Encoding Selected Caspases and MiRNAs Regulating their Expression in Endometrial Cancer Cell Line

Author(s):

Krzysztof Januszyk*, Piotr Januszyk, Beniamin Oskar Grabarek, Dariusz Boroń and Marcin Oplawski   Pages 1 - 11 ( 11 )

Abstract:


Background: Apoptosis could take place in the pathway dependent on death receptors or pathways dependent on mitochondria. In both, a key role is played by enzymes with protease activity, known as caspases.

Aim: The aim of this study was to assess the variances in the expression pattern of caspase-dependent signaling pathways in the endometrial cancer cell line when treated with salinomycin. Additionally, the changes in the level of miRNA that potentially regulate these mRNAs were evaluated.

Materials and Methods: Endometrial cancer cells were treated with 1 μM of salinomycin for 12, 24 and 48 hours. Untreated cells made up the control culture. The molecular analysis consisted of screening mRNA and miRNA microarray expression profiles of caspases, and the evaluation of the expression of caspases 3,8 and 9 by RTqPCR, also on the protein level.

Results: It was observed that 5 of the 14 differentiating mRNAs were commonly found for all incubation times of the cells and they corresponded with CASP3, CASP8, and CASP9 genes. The highest impact probability was determined between CASP3(up-regulated) and hsa- miR- 30d (FC -2.01), CASP8 (down-regulated) and hsa-miR-21 (FC +1.39) and between CASP9 (up-regulated) and hsa-miR-1271 (FC +1.71).

Conclusion: Salinomycin induces the apoptosis of endometrial cancer cells. The largest increase in activity was noted for caspases 3 and 9, while the expression of caspase 8 was decreased. Salinomycin causes a regulatory effect on the transcriptomes of mRNA and miRNA in in vitro endometrial cancer cells.

Keywords:

mitochondria-dependent and independent apoptosis pathway, salinomycin, endometrial cancer, miRNA, mRNA, microarray expression

Affiliation:

Faculty of Health Science, Public Higher Medical Professional School in Opole, Department of Gynecology and Obstetrics with Gynecologic Oncology, Ludwik Rydygier Memorial Specialized Hospital, Kraków, Maria Sklodowska-Curie National Research Institute of Oncology Krakow Branch, Department of Gynecology and Obstetrics with Gynecologic Oncology, Ludwik Rydygier Memorial Specialized Hospital, Kraków, Faculty of Health Science, Public Higher Medical Professional School in Opole



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