693175

MIR590

Over the last few decades, the epithelial-to-mesenchymal transition (EMT) has been identified as being involved in a number of aspects of physiological processes and various pathological events, including embryonic development and renal fibrosis. Transforming growth factorbeta receptor 2 (TGFbetaR2) is a widely studied gene, which fulfils a vital role in the TGFbeta signaling pathway and exerts a crucial function in the progression of EMT. Previous studies demonstrated that the dysregulation of microRNAs (miRNAs) is considered to be associated with the EMT process. However, the precise functional involvement of miRNAs in EMT remains to be fully elucidated. In the present study, the level of miR590 was decreased in an EMT model in vitro and in vivo. Furthermore, the overexpression of miR590 inhibited EMT by upregulating the epithelial marker, Ecadherin, and downregulating the mesenchymal markers, laminin, alphasmooth muscle actin (alphaSMA) and collagen, in the human kidney 2 (HK2) cell line. Furthermore, TGFbetaR2 was negatively regulated by miR590. In addition, performing a knockdown of TGFbetaR2 with smallinterfering RNA had an effect similar to miR590 on EMT in the HK2 cell line, whereas the transfection of pCMVtag2BTGFbetaR2 reversed the effect of miR590 on EMT in HK2 cells. Taken together, the present study demonstrated that miR-590 is a novel EMT-suppressive microRNA, which targets TGFbetaR2.

Invasion and migration of glioblastoma multiforme (GBM) is a multistep process and an important phenotype that causes this disease to invade surrounding tissues in the brain. The purpose of this study was to determine the role of miR-590-3p in regulation of epithelial mesenchymal transition (EMT) and metastasis of GBM cells. expression levels of miR-590-3p in 15 GBM specimens with adjacent tissues and five GBM cell lines were assessed by quantitative RT-PCR. We found that miR-590-3p was down-regulated in detected GBM tissue samples and all of the GBM cell lines. In addition, Ectopic expression of miR-590-3p suppressed and miR-590-3p-in promoted EMT, migration, and invasion in U87MG and A172 cells. Bioinformatics coupled with luciferase and Western blot assays also revealed that miR-590-3p inhibited expression of ZEB1 and ZEB2, which are master regulators of tumor metastasis. Our study first indicates that miR-590-3p functions as a suppressor of GBM EMT and metastasis by targeting ZEB1 and ZEB2, and it may be a therapeutic target for metastatic GBM.CI - Copyright (c) 2015 Elsevier Inc. All rights reserved.

The functional roles and clinical significances of miR-590-3p in ICC remain unclear. In the current study, we investigated the expression of miR-590-3p in tissues and sera of ICC by real-time quantitative polymerase chain reaction. We found miR-590-3p was significantly down-regulated in the sera and tissues of ICC patients, especially in those patients with lymph node metastasis or distant metastasis. AUC curves and Cox proportional hazards mode revealed serum miR-590-3p could be novel diagnostic and prognostic biomarker for ICC patients. MiR-590-3p dramatically suppressed epithelial-mesenchymal transition, cell migration, and invasion of ICC cells. SIP1 was identified as direct and functional target of miR-590-3p in ICC cells by luciferase assays. Finally, we found SIP1 expression was inversely correlated with miR-590-3p and closely related to diminished survival in ICC patients. These findings reveal functional and mechanistic roles of miR-590-3p and EMT activator SIP1 in the pathogenesis of ICC.