Department of Pathology, Peking Union Medical College Hospital, Beijing 100730, P. R. China.
Int J Oncol. 2020 Apr;56(4):1025-1033. doi: 10.3892/ijo.2020.4986. Epub 2020 Feb 14.
Pancreatic stellate cells (PSCs) are typically activated in pancreatic ductal adenocarcinoma (PDAC) and release exosomes containing high levels of microRNA‑21 (miR‑21). However, the specific roles of exosomal miR‑21 in regulating the PDAC malignant phenotype remain unknown. The present study aimed to determine the effects of exosomal miR‑21 on the migratory ability of PDAC cells and explore the potential underlying molecular mechanism. Weighted gene correlation network and The Cancer Genome Atlas database analysis revealed that high miR‑21 levels were associated with a poor prognosis in patients with pancreatic adenocarcinoma, and that the Ras/ERK signaling pathway may be a potential target of miR‑21. In vitro, PDAC cells were demonstrated to internalize the PSC-derived exosome, resulting in high miR‑21 levels, which subsequently promoted cell migration, induced epithelial‑to‑mesenchymal transition (EMT) and increased matrix metalloproteinase‑2/9 activity. In addition, exosomal miR‑21 increased the levels of ERK1/2 and Akt phosphorylation in PDAC cells. Collectively, these results suggested that PSC‑derived exosomal miR‑21 may promote PDAC cell migration and EMT and enhance Ras/ERK signaling activity. Thus, miR‑21 may be a potential cause of poor prognosis in patients with pancreatic cancer and a new treatment target.
胰腺星状细胞（PSCs）在胰腺导管腺癌（PDAC）中通常被激活，并释放含有高水平 microRNA-21（miR-21）的外泌体。然而，外泌体 miR-21 调节 PDAC 恶性表型的具体作用仍不清楚。本研究旨在确定外泌体 miR-21 对 PDAC 细胞迁移能力的影响，并探讨其潜在的分子机制。加权基因相关网络和癌症基因组图谱数据库分析表明，miR-21 水平高与胰腺腺癌患者预后不良相关，Ras/ERK 信号通路可能是 miR-21 的潜在靶点。在体外，PDAC 细胞被证明可以内化 PSC 来源的外泌体，导致 miR-21 水平升高，从而促进细胞迁移、诱导上皮-间充质转化（EMT）和增加基质金属蛋白酶-2/9 活性。此外，外泌体 miR-21 增加了 PDAC 细胞中 ERK1/2 和 Akt 磷酸化水平。综上所述，这些结果表明 PSC 来源的外泌体 miR-21 可能促进 PDAC 细胞迁移和 EMT，并增强 Ras/ERK 信号活性。因此，miR-21 可能是胰腺癌患者预后不良的潜在原因，也是一种新的治疗靶点。
