442891

MIR135B

Transcriptional co-activator with PDZ-binding motif (TAZ) is a WW domain-containing protein that regulates mesenchymal differentiation and organ development. It is also a downstream effector of the Hippo signaling pathway, which has been implicated in epithelial-mesenchymal transition (EMT) and tumorigenesis. However, the molecular mechanisms underlying TAZ function in these processes in the context of osteosarcoma (OS) are not well understood. We addressed this in the present study using U2OS and HOS cell lines. We found that TAZ signaling is maintained via a previously undescribed micro (mi)RNA-dependent positive feedback loop. The miRNA miR-135b, which is directly induced by TAZ, suppressed the TAZ inhibitors large tumor suppressor 2, adenomatous polyposis coli, and glycogen synthase kinase 3beta, thereby amplifying TAZ signaling and inducing EMT. Overexpression of miR-135b caused constitutive activation of TAZ, which rescued the inhibition of cell proliferation and EMT induced by TAZ knockdown. These results provide evidence that TAZ and miR-135b engage in a positive feedback loop to regulate EMT and metastasis in OS, and suggest that both factors can be therapeutic targets for OS treatment.CI - Copyright (c) 2017 Elsevier B.V. All rights reserved.

The exact mechanisms of metastasis for pancreatic cancer remain to be uncovered. This study aimed to elucidate the potential functional mechanism of miR-135b-5p in migration, invasion and epithelial-to-mesenchymal transition (EMT) of pancreatic cancer cells. By real-time PCR and analysis of GEO database, we determined the up-regulated expression of miR-135b-5p in pancreatic cancer tissues and cell lines. Clinically, highly expressed miR-135b-5p was closely related to advanced TNM stage, more lymph node metastasis, more distant metastasis and worse overall survival (OS) and disease-free survival (DFS). Functionally, Transwell assays indicated that miR-135b-5p was a promoter for migration and invasion of pancreatic cancer cells. Additionally, immunohistochemistry staining and Western blot showed that highly expressed miR-135b-5p accelerated EMT process of pancreatic cancer cells. Furthermore, a series of experiments and rescue experiments revealed that Nuclear Receptor Subfamily 3 Group C Member 2 (NR3C2) was the target of miR-135b-5p in pancreatic cancer cells, mediating the promotion effects of miR-135b-5p on the tumor cells migration, invasion and EMT. In conclusion, miR-135b-5p, maybe a novel therapeutic target for pancreatic cancer, promoted migration, invasion and EMT of pancreatic cancer cells by targeting NR3C2.CI - Copyright (c) 2017 Elsevier Masson SAS. All rights reserved.