Department of Molecular Cytogenetics, Medical Research Institute, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
Department of Digestive Surgery, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Sci Rep. 2017 Jun 21;7(1):4002. doi: 10.1038/s41598-017-04191-w.
The epithelial-mesenchymal transition (EMT) contributes to various processes in cancer progression, such as metastasis and drug resistance. Since we have already established a cell-based reporter system for identifying EMT-suppressive microRNAs (miRNAs) in the pancreatic cancer cell line Panc1, we performed a function-based screening assay by combining this reporter system and a miRNA library composed of 1,090 miRNAs. As a result, we identified miR-509-5p and miR-1243 as EMT-suppressive miRNAs, although the mechanisms for EMT-suppression induced by these miRNAs have yet to be clarified. Herein, we demonstrated that overexpression of miR-509-5p and miR-1243 increased the expression of E-cadherin through the suppression of EMT-related gene expression and that drug sensitivity increased with a combination of each of these miRNAs and gemcitabine. Moreover, miR-509-5p was associated with worse overall survival in patients with pancreatic cancer and was identified as an independently selected predictor of mortality. Our findings suggest that miR-509-5p and miR-1243 might be novel chemotherapeutic targets and serve as biomarkers in pancreatic cancer.
上皮-间充质转化（EMT）有助于癌症进展中的各种过程，例如转移和耐药性。由于我们已经在胰腺癌细胞系 Panc1 中建立了用于鉴定 EMT 抑制性 microRNA（miRNA）的基于细胞的报告系统，因此我们通过将该报告系统与由 1090 个 miRNA 组成的 miRNA 文库相结合，进行了基于功能的筛选测定。结果，我们鉴定出 miR-509-5p 和 miR-1243 是 EMT 抑制性 miRNA，尽管这些 miRNA 诱导 EMT 抑制的机制尚未阐明。在此，我们证明 miR-509-5p 和 miR-1243 的过表达通过抑制 EMT 相关基因的表达增加了 E-钙粘蛋白的表达，并且这些 miRNA 中的每一种与 gemcitabine 的组合均可增加药物敏感性。此外，miR-509-5p 与胰腺癌患者的总体生存不良相关，并被确定为死亡率的独立选择预测因子。我们的研究结果表明，miR-509-5p 和 miR-1243 可能是新的化疗靶标，并可作为胰腺癌的生物标志物。
