406925

MIR135A1

epithelial-mesenchymal transition (EMT) has been shown to be related to the pathogenesis of various diseases. Recently, microRNAs (miRNA) have been recognized as a new class of genes involved in human tumorigenesis. In this study, we found that the expression levels of miR-135a were dramatically decreased in NSCLC cell lines and clinical NSCLC tissue samples. Then, we demonstrated that miR-135a significantly suppressed the migration and invasion of lung cancer cells in vitro, suggesting that miR-135a may be a novel tumor suppressor. Further studies revealed that the transcription factor KLF8 was a target gene of miR-135a in NSCLC cells, as miR-135a bound directly to the 3'-untranslated region (3'-UTR) of KLF8, thus reducing both the expression of KLF8 at the mRNA and protein levels. In addition, the EMT marker E-cadherin or vimentin was also down-regulated or up-regulated on miR-135a treatment. Moreover, silencing KLF8 was able to inhibit the migration and invasion of lung cancer cells. In conclusion, these findings indicate that miR-135a suppresses the migration and invasion of NSCLC cells through targeting KLF8, which is involved in the EMT process. This finding provides new insight into the mechanism of NSCLC progression.CI - Copyright (c) 2015 Elsevier Inc. All rights reserved.

This study investigated the effects of microRNA-135a (miR-135a) targeting of glycogen synthase kinase 3beta (GSK3beta) on the epithelial-mesenchymal transition (EMT), migration and invasion of bladder cancer (BC) cells by mediating the Wnt/beta-catenin signaling pathway. BC and adjacent normal tissues were collected from 165 BC patients. Western blotting and quantitative real-time PCR were used to detect the expression of GSK3beta, beta-catenin, cyclinD1, E-cadherin, vimentin and miR-135a in BC tissues and cells. Cells were assigned to blank, negative control (NC), miR-135a mimics, miR-135a inhibitors, small interfering RNA (siRNA)-GSK3beta or miR-135a inhibitors+siRNA-GSK3beta groups. miR-135a, beta-catenin, cyclinD1 and vimentin expression increased, while GSK3beta and E-cadherin expression decreased in BC tissues compared with adjacent normal tissues. Compared with the blank and NC groups, the expression of miR-135a, beta-catenin, cyclinD1 and vimentin was higher, and cell proliferation, migration, invasion and tumor growth were increased in the miR-135a mimics and siRNA-GSK3beta groups. These groups showed an opposite trend in GSK3beta and E-cadherin expression and cell apoptosis. The miR-135a inhibitors group was inversely correlated with the blank and NC groups. It was concluded that miR-135a accelerates the EMT, invasion and migration of BC cells by activating the Wnt/beta-catenin signaling pathway through the downregulation of GSK3beta expression.