Faculty of Health Science, Public Higher Medical Professional School in Opole, Opole, Poland.
Department of Gynecology and Obstetrics with Gynecologic Oncology, Ludwik Rydygier Memorial Specialized Hospital, Krakow, Poland.
Curr Pharm Biotechnol. 2020;21(14):1505-1515. doi: 10.2174/1389201021666200514095043.
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.
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.
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.
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 (upregulated) and hsa-miR-1271 (FC +1.71).
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.
细胞凋亡可发生在依赖死亡受体的途径或依赖线粒体的途径中。在这两种途径中，具有蛋白酶活性的酶（称为半胱天冬酶）起着关键作用。
本研究旨在评估丝裂霉素处理子宫内膜癌细胞系时依赖半胱天冬酶信号通路的表达模式差异，并评估可能调节这些 mRNA 的 miRNA 水平的变化。
用 1μM 丝裂霉素处理子宫内膜癌细胞 12、24 和 48 小时。未处理的细胞作为对照培养。分子分析包括筛选半胱天冬酶的 mRNA 和 miRNA 微阵列表达谱，并通过 RTqPCR 评估半胱天冬酶 3、8 和 9 的表达，也在蛋白质水平上进行评估。
观察到 14 个差异表达的 mRNA 中有 5 个在细胞所有孵育时间中都普遍存在，它们与 CASP3、CASP8 和 CASP9 基因相对应。CASP3（上调）和 hsa-miR-30d（FC-2.01）、CASP8（下调）和 hsa-miR-21（FC+1.39）以及 CASP9（上调）和 hsa-miR-1271（FC+1.71）之间的概率最高。
丝裂霉素诱导子宫内膜癌细胞凋亡。活性增加最大的是半胱天冬酶 3 和 9，而半胱天冬酶 8 的表达降低。丝裂霉素对体外子宫内膜癌细胞的 mRNA 和 miRNA 转录组产生调节作用。
