Januszyk Szymon, Mieszczański Paweł, Lurka Hubert, Sagan Dorota, Boroń Dariusz, Grabarek Beniamin Oskar
ICZ Healthcare Hospital in Zywiec, 34-300 Zywiec, Poland.
Hospital of Ministry of Interior and Administration, 40-052 Katowice, Poland.
Biomedicines. 2022 May 20;10(5):1190. doi: 10.3390/biomedicines10051190.
The oxidative stress phenomenon is a result of anticancer therapy. The aim of this study was the assessment of gene expression profile changes, and to determine the miRNAs regulating genes' transcriptional activity in an Ishikawa endometrial cancer culture exposed to cisplatin or salinomycin, compared to a control culture. The molecular analysis comprised the microarray technique (mRNAs and micro RNA (miRNA), the real-time quantitative reverse transcription reaction (RTqPCR), enzyme-linked immunosorbent assay (ELISA) reactions, and Western blot. NR4A2, MAP3K8, ICAM1, IL21, CXCL8, CCL7, and SLC7A11 were statistically significantly differentiated depending not only on time, but also on the drug used in the experiment. The conducted assessment indicated that the strongest links were between NR4A2 and hsa-miR-30a-5p and has-miR-302e, MAP3K8 and hsa-miR-144-3p, CXCL8 and hsa-miR-140-3p, and SLC7A11 and hsa-miR-144-3p. The obtained results suggest that four mRNAs-NR4A2, MAP3K8, CXCL8 and SLC7A11-and four miRNAs-hsa-miR-30a-5p, hsa-miR-302e, hsa-miR-144-3p and hsa-miR-140-3-changed their expressions regardless of the chemotherapeutic agent used, which suggests the possibility of their use in monitoring the severity of oxidative stress in endometrial cancer. However, considering the results at both the mRNA and the protein level, it is most likely that the expressions of NR4A2, MAP3K8, CXCL8 and SLC7A11 are regulated by miRNA molecules as well as other epigenetic mechanisms.
氧化应激现象是抗癌治疗的结果。本研究的目的是评估基因表达谱的变化，并确定与对照培养相比，在暴露于顺铂或沙利霉素的石川子宫内膜癌培养物中调节基因转录活性的微小RNA（miRNA）。分子分析包括微阵列技术（mRNA和微小RNA（miRNA））、实时定量逆转录反应（RTqPCR）、酶联免疫吸附测定（ELISA）反应和蛋白质印迹法。NR4A2、MAP3K8、ICAM1、IL21、CXCL8、CCL7和SLC7A11不仅在时间上，而且在实验中使用的药物方面都有统计学上的显著差异。所进行的评估表明，最强的联系存在于NR4A2与hsa-miR-30a-5p和hsa-miR-302e之间、MAP3K8与hsa-miR-144-3p之间、CXCL8与hsa-miR-140-3p之间以及SLC7A11与hsa-miR-144-3p之间。获得的结果表明，四种mRNA（NR4A2、MAP3K8、CXCL8和SLC7A11）和四种miRNA（hsa-miR-30a-5p、hsa-miR-302e、hsa-miR-144-3p和hsa-miR-140-3）的表达无论使用何种化疗药物都会发生变化，这表明它们有可能用于监测子宫内膜癌氧化应激的严重程度。然而，考虑到mRNA和蛋白质水平的结果，NR4A2、MAP3K8、CXCL8和SLC7A11的表达很可能受miRNA分子以及其他表观遗传机制的调节。
