Wang Jue, Zhang Youli, Wei Hong, Zhang Xingxing, Wu Yan, Gong Aihua, Xia Yu, Wang Wenbing, Xu Min
Department of Gastroenterology, Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang 212000, China.
Department of Cell Biology, School of Medicine, Jiangsu University, Zhenjiang 212000, China.
Oncotarget. 2017 Apr 11;8(15):24978-24987. doi: 10.18632/oncotarget.15330.
Pancreatic cancer (PC) is a highly lethal disease due to extensive metastatic lesions. Accumulating evidence suggests that miR-675-5p plays different roles in metastasis through the regulation of epithelial to mesenchymal (EMT) and the mesenchymal to epithelial transitions (MET) in different cancers. ZEB1 promotes the EMT process by controlling the expression of E-cadherin and may have a reciprocal regulation with Ubiquilin1 (UBQLN1) and mir-200 family in cancer progression. In the present study, we showed that decreased expression of miR-675-5p is associated with the enhanced cell proliferation and survival of PC cells, while the increased expression of mir-675-5p shows the opposite one. The mir-675-5p could decrease the expression of mir-200 which is intermediated by ZEB1, and increase the expression of UBQLN1 gene. The mir-675-5p can increase the expression of ZEB1 mRNA, but the ZEB1 protein level was decreased. When mir-675-5p mimics and siUBQLN1 were co-transfected into the pancreatic cancer Patu8988 cells, the expression of ZEB1 protein was increased. It suggests that mir-675-5p may affect ZEB1 in a post-transcriptional level which was verified to be regulated by UBQLN1 protein. Hence, mir-675-5p regulates the progression of pancreatic cancer cells through the UBQLN1-ZEB1-mir200 pathway.
胰腺癌（PC）是一种因广泛转移灶而具有高度致死性的疾病。越来越多的证据表明，miR - 675 - 5p在不同癌症中通过调节上皮 - 间质转化（EMT）和间质 - 上皮转化（MET）在转移过程中发挥不同作用。ZEB1通过控制E - 钙黏蛋白的表达促进EMT过程，并且在癌症进展中可能与泛素连接酶1（UBQLN1）和mir - 200家族存在相互调节关系。在本研究中，我们发现miR - 675 - 5p表达降低与胰腺癌细胞的增殖和存活增强相关，而mir - 675 - 5p表达增加则呈现相反情况。mir - 675 - 5p可降低由ZEB1介导的mir - 200的表达，并增加UBQLN1基因的表达。mir - 675 - 5p可增加ZEB1 mRNA的表达，但ZEB1蛋白水平降低。当将mir - 675 - 5p模拟物和siUBQLN1共转染到胰腺癌Patu8988细胞中时，ZEB1蛋白的表达增加。这表明mir - 675 - 5p可能在转录后水平影响ZEB1，且已证实这一过程受UBQLN1蛋白调控。因此，mir - 675 - 5p通过UBQLN1 - ZEB1 - mir200途径调节胰腺癌细胞的进展。
