Xiong Junjie, Wang Dan, Wei Ailin, Lu Huimin, Tan Chunlu, Li Ang, Tang Jie, Wang Yichao, He Sirong, Liu Xubao, Hu Weiming
Department of Pancreatic Surgery, West China Hospital of Sichuan University, Chengdu 610041, China.
Department of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University, Chengdu 610041, China.
Exp Cell Res. 2017 Dec 15;361(2):316-323. doi: 10.1016/j.yexcr.2017.10.033. Epub 2017 Oct 28.
Pancreatic ductal adenocarcinoma (PDAC) displays a highly aggressive malignancy and is considered to be an incurable and rapidly lethal disease. MicroRNAs (miRNAs) are small non-coding RNAs of approximately nucleotides that regulate several aspects of tumors pathogenesis, including migration, invasion, metastasis and epithelial-mesenchymal transition. We have found that miR-107 was significantly high expression in PDAC tissues and cells. High miR-107 expression is associated with poor clinicopathological parameters and prognosis in PDAC patients. Deregulated expression of miR-107 in PDAC cells (AsPC-1 and Panc-1) is sufficient to reduce cell migration and invasion, and to induce upregulation of epithelial markers (β-catenin, ZO-1 and E-cadherin) and a decrease of mesenchymal marker expression (ZEB-1 and vimentin). We also found that the caveolin-1, PTEN and p-Akt expression are modulated by miR-107 in PDAC cells. Moreover, our study clearly demonstrated that deregulated expression of miR-107 inhibited cell migration and invasion and EMT by up-regulation of caveolin-1 and PTEN, and inhibition of PI3K/Akt signaling in PDAC cells. Our study suggested that miR‑107 expression might both be a useful indicator of the metastatic potential and provided a new potential therapeutic target in PDAC.
胰腺导管腺癌（PDAC）具有高度侵袭性的恶性特征，被认为是一种无法治愈且致死率高的疾病。微小RNA（miRNA）是一类约含22个核苷酸的小型非编码RNA，可调节肿瘤发病机制的多个方面，包括迁移、侵袭、转移和上皮-间质转化。我们发现miR-107在PDAC组织和细胞中显著高表达。miR-107高表达与PDAC患者不良的临床病理参数及预后相关。在PDAC细胞（AsPC-1和Panc-1）中，miR-107表达失调足以降低细胞迁移和侵袭能力，并诱导上皮标志物（β-连环蛋白、紧密连接蛋白1和E-钙黏蛋白）上调以及间充质标志物表达（锌指蛋白E盒结合因子1和波形蛋白）降低。我们还发现，在PDAC细胞中，小窝蛋白-1、PTEN和磷酸化Akt的表达受miR-107调控。此外，我们的研究清楚地表明，miR-107表达失调通过上调小窝蛋白-1和PTEN以及抑制PI3K/Akt信号通路，抑制了PDAC细胞的迁移、侵袭和上皮-间质转化。我们的研究表明，miR-107表达可能既是转移潜能的有用指标，也为PDAC提供了一个新的潜在治疗靶点。
