The mir-675-5p regulates the progression and development of pancreatic cancer via the UBQLN1-ZEB1-mir200 axis
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Jue Wang1,*, Youli Zhang1,*, Hong Wei1, Xingxing Zhang1, Yan Wu3, Aihua Gong3, Yu Xia1, Wenbing Wang2, Min Xu1
1Department of Gastroenterology, Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang 212000, China
2Department of Public Health, School of Medicine, Jiangsu University, Zhenjiang 212000, China
3Department of Cell Biology, School of Medicine, Jiangsu University, Zhenjiang 212000, China
*These authors have contributed equally to this work
Wenbing Wang, email: [email protected]
Min Xu, email: [email protected]
Keywords: Mir-675, mir-200, ZEB1, UBQLN1, pancreatic cancer progression
Received: June 30, 2016 Accepted: January 19, 2017 Published: February 15, 2017
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.
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