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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.
Current Pharmaceutical Biotechnology ( IF 2.2 ) Pub Date : 2020-10-31 , DOI: 10.2174/1389201021666200514095043
Krzysztof Januszyk 1 , Piotr Januszyk 2 , Beniamin O Grabarek 3 , Dariusz Boroñ 3 , Marcin Oplawski 1
Affiliation  

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 and Discussion: 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).

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.



中文翻译:

盐霉素对编码所选 Caspases 的 mRNA 和调节其在子宫内膜癌细胞系中表达的 miRNA 的表达谱的影响。

背景:细胞凋亡可能发生在依赖死亡受体的途径或依赖线粒体的途径中。在这两种情况下,具有蛋白酶活性的酶(称为半胱天冬酶)发挥着关键作用。

目的:本研究的目的是评估子宫内膜癌细胞系用盐霉素处理时 caspase 依赖性信号通路表达模式的差异。此外,还评估了可能调节这些 mRNA 的 miRNA 水平的变化。

材料和方法:子宫内膜癌细胞用 1 μM 盐霉素处理 12、24 和 48 小时。未处理的细胞构成对照培养物。分子分析包括筛选 caspase 的 mRNA 和 miRNA 微阵列表达谱,以及通过 RTqPCR 评估 caspase 3,8 和 9 的表达(也在蛋白质水平上)。

结果和讨论:据观察,14 个分化 mRNA 中有 5 个在细胞的所有孵育时间中常见,并且它们与 CASP3、CASP8 和 CASP9 基因相对应。最高影响概率确定在 CASP3(上调)和 hsa-miR-30d (FC -2.01)、CASP8(下调)和 hsa-miR-21 (FC +1.39) 之间以及 CASP9(上调)和 hsa 之间-miR-1271(FC +1.71)。

结论:盐霉素可诱导子宫内膜癌细胞凋亡。半胱天冬酶 3 和 9 的活性增加最多,而半胱天冬酶 8 的表达下降。Salinomycin 对体外子宫内膜癌细胞中 mRNA 和 miRNA 的转录组产生调节作用。

更新日期:2020-12-07
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