494323

MIR361

MicroRNA-361-5p (miR-361-5p) has been reported to be dysregulated in various human cancer types. However, the function of miR-361-5p in glioma remains unknown. In the present study, we aimed to investigate the biological functions of miR-361-5p in regulating glioma progression and the underlying molecular mechanism. We found that miR-361-5p was significantly decreased in glioma tissues and cell lines as detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis. Functional analysis revealed that miR-361-5p overexpression significantly inhibited glioma cell migration, invasion and epithelial-mesenchymal transition (EMT) whereas suppression of miR-361-5p showed opposite effects. Bioinformatic analysis showed that Twist1, a critical EMT inducer, was a predicted target of miR-361-5p which was validated by dual-luciferase reporter assay, RT-qPCR and western blot analysis. Further analysis indicated that miR-361-5p regulates the Twist1/Bmi-1 signaling axis. Rescue experiments showed that restoration of Twist1 expression significantly reversed the suppressive effect of miR-361-5p on cell migration, invasion and EMT. Taken together, the present study demonstrated an important role of miR-361-5p in glioma - which regulated the EMT of glioma cells by targeting and regulating Twist1. These findings provide novel insight into understanding the role and mechanism of miR-361-5p in regulating the biolo-gical behavior of glioma cells and suggest that miR-361-5p is a novel potential therapeutic target for glioma.

Epithelia-mesenchymal transition (EMT) is critical for invasion and metastasis of esophageal carcinoma. Gli1, a transcriptional factor in Hedgehog pathway, is correlated with EMT, invasion and metastasis of tumors. However, its role in esophageal cancer is still unknown. Bioinformatics analysis revealed relationship between microRNA (miR)-361 and 3'-UTR of Gli1 gene. This study thus investigated the role of miR-361 and Gli1 in invasion and metastasis of esophageal cancer. Both tumor and adjacent tissues were collected from 58 esophageal cancer patients to test the expressions of miR-361 and Gli1, the relationship of which was confirmed by dual-luciferase reporter gene assay. Cultured esophageal cancer cells EC9706 were transfected with mimic NC, miR-361 mimic, si-NC, si-Gli1, miR-361 mimics+si-Glil, pQC or pQC-FU-Gli1. Transwell and colony formation assays were performed for cell invasion and attachment-independent growth. expressions of Gli1, Snail, E-cadherin and N-cadherin proteins were revealed by Western blotting. The expression of Gli1 was significantly elevated in esophageal cancer tissues, along with lower miR-361 expression which was correlated with TNM stage. MiR-361 inhibited the expression of Gli1 via targeting on 3'-UTR of Gli1 gene. The transfection of miR-361 mimics and/or si-Gli1 significantly suppressed the growth of malignant cells. The over-expression of miR-361 and/or silencing of Gli1 decreased intracellular expression of Gli1, Snail and N-cadherin, and increased E-cadherin expression to suppress EMT and invasion of tumor cells while the opposite effects were obtained by over-expression of Gli1. Abnormal elevation of Gli1 and decrease of miR-361 were found in esophageal cancer tissues. MiR-361 weakened invasion of cancer cells and impeded EMT process via the inhibition of Gli1.

MiR-361-5p has been reported to be dysregulated in several types of cancers. However, the function of miR-361-5p in gastric cancer (GC) is still not clear. In our present study, we aimed to investigate the effects of miR-361-5p in the mobility of GC and its potential mechanism. We found that miR-361-5p was significantly decreased in GC cell lines and tumor tissues. Decreased miR-361-5p expression was correlated with larger tumor size and advanced TNM stage. Functional analysis revealed that overexpression of miR-361-5p inhibited cell proliferation and mobility through suppressing the expression of MMP-3, MMP-9 and VEGF. Moreover, the expression of epithelial marker E-cadherin was increased while the expression of mesenchymal marker (Snail, N-cadherin, b-catenin) and Wnt/beta-catenin pathway related proteins (TCF4, Cyclin-D1, c-Myc) was increased by overexpression of miR-361-5p, indicating that overexpression of miR-361-5p suppressed epithelial-mesenchymal transition (EMT) via inhibiting Wnt/beta-catenin pathway in GC cells. In order to further verify our conjecture that miR-361-5p mimic inhibited cell mobility through suppressing EMT via Wnt/beta-catenin pathway in GC, the Wnt/beta-catenin pathway activator LiCl was used in this study. Our data showed that activation of Wnt/beta-catenin pathway by LiCl counteracted the regulating roles of miR-361-5p mimic through promoting EMT and cell mobility. In addition, TCF4 was knockdown and overexpressed in GC cells, and the results convinced the involvement of Wnt pathway in the regulation of EMT. Finally, results from in vivo experiments suggested that overexpression of miR-361-5p suppressed tumor growth and the expression of VEGF markedly through inhibiting EMT via the Wnt/beta-catenin pathway in GC nude mice. Taken together, our in vitro and in vivo experiments indicated that miR-361-5p suppressed cell mobility in GC through the inhibition of EMT via Wnt/beta-catenin pathway. Our findings indicated that miR-361-5p could be a promising therapeutic target for GC treatment.CI - Copyright (c) 2018 Elsevier B.V. All rights reserved.