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Expression Profile of EMT-related Genes and miRNAs Involved in Signal Transduction via the Wnt Pathway and Cadherins in Endometrial Cancer
Current Pharmaceutical Biotechnology ( IF 2.2 ) Pub Date : 2021-09-30 , DOI: 10.2174/1389201021666201218125900
Nikola Zmarzły 1 , Ewelina Hermyt 2 , Celina Kruszniewska-Rajs 3 , Joanna Gola 3 , Andrzej Witek 2 , Urszula Mazurek 4 , Aleksander Ostenda 5 , Dariusz Boroń 1
Affiliation  

Background: Epithelial-Mesenchymal Transition (EMT) is a molecular reprogramming that leads to an increased ability to migrate, which can promote invasion and metastasis. EMT can be initiated in response to the activity of signaling pathways such as Wnt as well as miRNAs.

Objective: The aim of the study was to determine the expression profile of EMT-related genes involved in signal transduction via the Wnt pathway and cadherins and to assess which miRNAs can participate in the regulation of their expression.

Methods: The study material consisted of 50 endometrial samples: 40 with diagnosed endometrial cancer and 10 without neoplastic changes. The expression profile of EMT-related genes was assessed with microarrays and validated by RT-qPCR. MicroRNA expression profiling was performed using microarrays. It was also determined which miRNAs may participate in the expression regulation of EMT-related genes.

Results: CDH1 overexpression was observed in all three endometrial cancer grades using both mRNA microarrays and RT-qPCR. The microarray experiment showed a decrease in CDH2 level regardless of the endometrial cancer grade, however, it was only partially validated with RT-qPCR. Low levels of WNT2, WNT4, WNT5A have also been observed. Decreased expression of WNT2 and WNT5A may be caused by miR-331-3p and miR-200b-5p, respectively.

Conclusion: The Wnt signaling is disrupted in endometrial cancer, which may be due to miR-331- 3p and miR-200b-5p activity. In addition, a change in WNT5A level in endometrial cancer compared to control may indicate that it acts as a suppressor gene and that its low expression is associated with tumor progression.



中文翻译:

子宫内膜癌中通过 Wnt 通路和钙粘蛋白参与信号转导的 EMT 相关基因和 miRNA 的表达谱

背景:上皮间质转化 (EMT) 是一种分子重编程,可导致迁移能力增强,从而促进侵袭和转移。EMT 可以响应 Wnt 和 miRNA 等信号通路的活性而启动。

目的:本研究的目的是确定通过 Wnt 通路和钙粘蛋白参与信号转导的 EMT 相关基因的表达谱,并评估哪些 miRNA 可以参与其表达的调节。

方法:研究材料由 50 个子宫内膜样本组成:40 个诊断为子宫内膜癌,10 个没有肿瘤变化。用微阵列评估 EMT 相关基因的表达谱,并通过 RT-qPCR 验证。MicroRNA 表达谱使用微阵列进行。还确定了哪些miRNA可能参与EMT相关基因的表达调控。

结果:使用 mRNA 微阵列和 RT-qPCR 在所有三个子宫内膜癌等级中都观察到 CDH1 过表达。微阵列实验显示,无论子宫内膜癌分级如何,CDH2 水平都会降低,但是,RT-qPCR 仅部分验证了这一点。还观察到低水平的 WNT2、WNT4、WNT5A。WNT2 和 WNT5A 的表达降低可能分别由 miR-331-3p 和 miR-200b-5p 引起。

结论:Wnt信号在子宫内膜癌中被破坏,这可能是由于miR-331-3p和miR-200b-5p的活性。此外,与对照相比,子宫内膜癌中 WNT5A 水平的变化可能表明它充当抑制基因,并且其低表达与肿瘤进展相关。

更新日期:2021-09-02
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