The mir-675-5p regulates the progression and development of pancreatic cancer via the UBQLN1-ZEB1-mir200 axis

Abstract

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.