子宫内膜癌细胞系 EMT 相关基因表达谱的变异性：体外研究。

Variances in the Expression Profile of the EMT-Related Genes in Endometrial Cancer Lines In Vitro Study.

机构信息

Department of Histology, Cytophysiology, and Embryology, Faculty of Medicine, the University of Technology in Katowice, 41-800 Zabrze, Poland | The District Hospital in Chrzanów, 32-500 Chrzanów, Poland | Department of Gynecology and Obstetrics with Gynecologic Oncology, Ludwik Rydygier Memorial Specialized Hospital, 31-826 Kraków, Poland.

出版信息

Curr Pharm Biotechnol. 2022;23(4):594-608. doi: 10.2174/1389201022666210702153919.

DOI:10.2174/1389201022666210702153919

PMID:34225617

Abstract

BACKGROUND

The aim of the study was to evaluate the variances in the expression pattern of mRNAs and miRNAs related to the EMT in the Ishikawa (histological grade 1; G1), EC-1A (histological grade 2; G2), and KLE (histological grade 3; G3) cell cultures under cisplatin treatment.

METHODS

Endometrial cancer cell lines were exposed to 75.22 mg (an average concentration of the drug used in patients with endometrial cancer) for 12.24 and 48 hours in comparison to the untreated cells (control). The molecular analysis included: extraction of total RNA, microarray analysis (mRNA and miRNA), RTqPCR, and the ELISA assay.

RESULTS

Out of 226 mRNAs associated with the EMT, the number of mRNAs differentially expressed in endometrial cancer cell cultures treated with cisplatin compared to a control culture was as follows: Ishikawa line - 87 mRNAs; EC-1A - 84 mRNAs; KLE - 71 mRNAs (p<0.05). The greatest changes in the Ishikawa line treated with the drug compared to the control were noticed for mRNA STAT1 TGFβ1, SMAD3, FOXO8, whereas in EC-1A they were mRNA TGFβ1, BAMBI, SMAD4, and in KLE mRNA COL1A1, FOXO8, TGFβ1. The analysis also showed that miR-106a, miR-30d, miR-300 are common for all cell lines used in this experiment.

CONCLUSION

Cisplatin changes the expression profile of genes associated with EMT in endometrial cancer cell lines. It seems that the expression pattern of TGFβ1 might be a promising, supplementary molecular marker of the effectiveness of cisplatin therapy. The analysis showed that miR-30d, miR-300, and miR-106a are involved in the regulation of the expression of EMT-related genes.

摘要

背景

本研究旨在评估顺铂处理后，在 Ishikawa（组织学 1 级；G1）、EC-1A（组织学 2 级；G2）和 KLE（组织学 3 级；G3）细胞培养物中，与 EMT 相关的 mRNAs 和 miRNAs 的表达模式差异。

方法

将子宫内膜癌细胞系暴露于 75.22mg（用于治疗子宫内膜癌患者的药物平均浓度）中 12.24 和 48 小时，与未经处理的细胞（对照）进行比较。分子分析包括：总 RNA 提取、微阵列分析（mRNA 和 miRNA）、RTqPCR 和 ELISA 检测。

结果

在与 EMT 相关的 226 个 mRNAs 中，与顺铂处理的子宫内膜癌细胞培养物相比，未经处理的细胞培养物中差异表达的 mRNAs 数量如下：Ishikawa 系 - 87 个 mRNAs；EC-1A - 84 个 mRNAs；KLE - 71 个 mRNAs（p<0.05）。与对照组相比，用药物处理的 Ishikawa 系中变化最大的 mRNAs 是 STAT1 TGFβ1、SMAD3、FOXO8，而在 EC-1A 中则是 TGFβ1、BAMBI、SMAD4，在 KLE 中则是 COL1A1、FOXO8、TGFβ1。分析还表明，miR-106a、miR-30d、miR-300 是本实验中所有细胞系共有的。