Liu Huaize, Wang Han, Liu Xiaoxiao, Yu Tingting
Department of Developmental Genetics, Nanjing Medical University, Nanjing 210029, PR China.
The First Clinical Medical College of Nanjing Medical University, Nanjing 210029, PR China.
Biochem Biophys Res Commun. 2016 Apr 1;472(2):346-52. doi: 10.1016/j.bbrc.2016.02.096. Epub 2016 Mar 3.
Pancreatic cancer (PC) remains one of the most lethal types of cancer in adults. The purpose of this study was to determine the role of miR-1271 in regulation of epithelial mesenchymal transition (EMT) and metastasis of pancreatic cancer cells. miR-1271 was identified to be significantly down-regulated in PC tissues by miRNA array. Also, an increase of EMT-regulators ZEB1 and TWIST1 expression level is accompanied by a decrease of miR-1271. We showed that expression of miR-1271 was significantly down-regulated in PC tissues as compared with that in normal tissues. In addition, our results showed that miR-1271 expression levels were decreased while ZEB1 and TWIST1 expression levels were increased in detected PC cell lines. Moreover, ectopic expression of miR-1271 suppressed and antagomiR-1271 promoted proliferation, migration, and invasion in SW1990 and PANC-1 cells. Bioinformatics coupled with luciferase and Western blot assays also revealed that miR-1271 inhibited expression of ZEB1 and TWIST1, which are master regulators of tumor metastasis. Our study first indicates that miR-1271 functions as a suppressor in regulating of pancreatic cancer EMT by targeting ZEB1 and TWIST1, and it promise as a therapeutic target and prognostic marker for metastatic pancreatic cancer.
胰腺癌(PC)仍然是成人中最致命的癌症类型之一。本研究的目的是确定miR-1271在调节胰腺癌细胞上皮-间质转化(EMT)和转移中的作用。通过miRNA阵列鉴定出miR-1271在PC组织中显著下调。此外,EMT调节因子ZEB1和TWIST1表达水平的增加伴随着miR-1271的减少。我们发现,与正常组织相比,miR-1271在PC组织中的表达显著下调。此外,我们的结果显示,在检测的PC细胞系中,miR-1271表达水平降低,而ZEB1和TWIST1表达水平升高。此外,miR-1271的异位表达抑制,而抗miR-1271促进SW1990和PANC-1细胞的增殖、迁移和侵袭。生物信息学结合荧光素酶和蛋白质印迹分析还显示,miR-1271抑制ZEB1和TWIST1的表达,而ZEB1和TWIST1是肿瘤转移的主要调节因子。我们的研究首次表明,miR-1271通过靶向ZEB1和TWIST1在调节胰腺癌EMT中起抑制作用,有望成为转移性胰腺癌的治疗靶点和预后标志物。