Institute of Medical Biology, PAS, 106 Lodowa Street, 93232, Lodz, Poland.
Sci Rep. 2019 Feb 15;9(1):2165. doi: 10.1038/s41598-019-39200-7.
Epithelial-to-mesenchymal transition (EMT) in cancer cells, represents early stages of metastasis and is a promising target in colorectal cancer (CRC) therapy. There have been many attempts to identify markers and key pathways induced throughout EMT but the process is complex and depends on the cancer type and tumour microenvironment. Here we used the colon cancer cell line HT29, which stably overexpressed Snail, the key transcription factor in early EMT, as a model for colorectal adenocarcinoma cells with a pro-metastatic phenotype. We investigated miRNA expression regulation during that phenotypic switching. We found that overexpression of Snail in HT29 cells triggered significant changes in individual miRNA levels but did not change the global efficiency of miRNA processing. Snail abundance repressed the expression of miR-192 and miR-194 and increased miR-205, let-7i and SNORD13 levels. These identified changes correlated with the reported transcriptomic alterations in Snail-overexpressing HT29 cells. We also investigated how Snail affected the miRNA content of extracellular vesicles (EVs) released from HT29 cells. Our data suggest that the presence of Snail significantly alters the complex mRNA/miRNA interactions in the early steps of metastasis and also has an impact on the content of EVs released from HT29 cells.
上皮-间充质转化（EMT）在癌细胞中代表转移的早期阶段，是结直肠癌（CRC）治疗的一个有前途的靶点。已经有许多尝试来识别 EMT 过程中诱导的标志物和关键途径，但该过程很复杂，取决于癌症类型和肿瘤微环境。在这里，我们使用稳定过表达 Snail 的结肠癌细胞系 HT29 作为具有促转移表型的结直肠腺癌细胞模型，Snail 是 EMT 早期的关键转录因子。我们研究了 EMT 过程中 miRNA 表达调控。我们发现，Snail 在 HT29 细胞中的过表达引发了个别 miRNA 水平的显著变化，但并未改变 miRNA 加工的整体效率。Snail 丰度抑制了 miR-192 和 miR-194 的表达，并增加了 miR-205、let-7i 和 SNORD13 的水平。这些鉴定出的变化与 Snail 过表达 HT29 细胞中的转录组改变相关。我们还研究了 Snail 如何影响 HT29 细胞释放的细胞外囊泡（EVs）中的 miRNA 含量。我们的数据表明，Snail 的存在显著改变了转移早期复杂的 mRNA/miRNA 相互作用，并且对 HT29 细胞释放的 EVs 的内容也有影响。
