Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan.
Biochem Biophys Res Commun. 2013 Aug 2;437(3):433-9. doi: 10.1016/j.bbrc.2013.06.097. Epub 2013 Jul 4.
There is accumulating evidence that pancreatic stellate cells (PSCs) promote the progression of pancreatic cancer. microRNAs (miRNAs) are small non-coding RNAs acting as negative regulators of gene expression at the post-transcriptional level. This study aimed to clarify the role of miRNAs in the interaction between PSCs and pancreatic cancer cells. Pancreatic cancer cells were mono-cultured or indirectly co-cultured with PSCs. miRNAs were prepared, and Agilent's miRNA microarray containing probes for 904 human miRNAs was used to identify differentially expressed miRNAs. miR-210 was identified as an upregulated miRNA by co-culture with PSCs. Conditioned media of PSCs activated ERK and Akt, but not hypoxia-inducible factor-1α pathway. PSCs-induced miR-210 upregulation was inhibited by inhibitors of ERK and PI3K/Akt pathways. Inhibition of miR-210 expression decreased migration, decreased the expression of vimentin and snai-1, and increased the membrane-associated expression of β-catenin in Panc-1 cells co-cultured with PSCs. In conclusion, our results suggest a novel role of miR-210 in the interaction between PSCs and pancreatic cancer cells.
越来越多的证据表明胰腺星状细胞（PSCs）促进胰腺癌的进展。微小 RNA（miRNA）是一种小的非编码 RNA，作为转录后水平基因表达的负调控因子。本研究旨在阐明 miRNA 在 PSCs 与胰腺癌细胞相互作用中的作用。胰腺癌细胞单独培养或与 PSCs 间接共培养。提取 miRNA，使用包含 904 个人类 miRNA 探针的 Agilent miRNA 微阵列来鉴定差异表达的 miRNA。与 PSCs 共培养后，miR-210 被鉴定为上调 miRNA。PSCs 激活 ERK 和 Akt，但不激活缺氧诱导因子-1α途径。PSCs 诱导的 miR-210 上调被 ERK 和 PI3K/Akt 途径抑制剂抑制。抑制 miR-210 的表达降低了 Panc-1 细胞的迁移，降低了波形蛋白和 snai-1 的表达，并增加了与 PSCs 共培养的 Panc-1 细胞中 β-连环蛋白的膜相关表达。总之，我们的结果表明 miR-210 在 PSCs 与胰腺癌细胞相互作用中具有新的作用。
