Effects of microRNA-183 on epithelial-mesenchymal transition, proliferation, migration, invasion and apoptosis in human pancreatic cancer SW1900 cells by targeting MTA1.

This study aims to explore effects of miR-183 on epithelial-mesenchymal transition (EMT) and invasion by targeting MTA1 in human pancreatic cancer (PC) cells. Totally, 108 PC patients admitted in Wenzhou Central Hospital and Wenzhou People's Hospital, The Dingli Clinical Institute of Wenzhou Medical University from March 2010 to March 2014 were enrolled. qRT-PCR and immunohistochemistry were applied to examine expression of MTA1 mRNA and protein. Samples were divided into 6 groups: blank, NC, miR-183 mimics, miR-183 inhibitors, MTA1-siRNA and miR-183 inhibitors +MTA1-siRNA groups. CCK8 method was employed for determining cell proliferation rate, flow cytometry for cell apoptosis rate, scratch test for cell migration and Transwell assay for cell invasion. qRT-PCR and Western blotting were used to determine expression of MTA1, E-cadherin and Vimentin mRNA and protein. Positive expression rate of MTA1 was upregulated in PC tissues, and expression of miR-183 and MTA1 was associated with differentiation, migration, tumor size, TNM. The miR-183 mimics and MTA1-siRNA groups showed a decrease in proliferation, migration and invasion, whereas increased apoptosis, in comparison with blank and NC groups, as expression of MTA1 and Vimentin mRNA and protein were reduced, expression of E-cadherin mRNA and protein was elevated. Compared to blank and NC groups, the miR-183 inhibitors group exhibited enhanced proliferation, migration and invasion and inhibited apoptosis; increased expressions of MTA1 and Vimentin mRNA and protein and decreased expressions of E-cadherin mRNA and protein. Our study supported that miR-183 could repress EMT and invasion of human PC cells through inhibition of MTA1 expression.

Lin X ，Zheng L ，Song H ，Xiao J ，Pan B ，Chen H ，Jin X ，Yu H ... -  《-》

MicroRNA-183 Acts as a Tumor Suppressor in Human Non-Small Cell Lung Cancer by Down-Regulating MTA1.

MicroRNAs (miRs) often contribute to the progression of non-small cell lung cancer (NSCLC) via regulation of mRNAs that are involved in lung homeostasis. We conducted a study aimed at exploring the roles of miR-183 in the proliferation, epithelial-mesenchymal transition (EMT), invasion and migration of human NSCLC cells via targeting MTA1. NSCLC and adjacent normal tissues were collected from 194 patients with NSCLC. Positive expression of MTA1 protein was detected by immunohistochemistry. The highest levels of expression of miR-183 were detected using RT-qPCR in SPC-A-1 cells, which were selected and assigned to the following groups: blank, negative control (NC), miR-183 mimic, miR-183 inhibitor, siRNA-MTA1, and miR-183 inhibitor + siRNA-MTA1. The expression of miR-183 and the mRNA and protein expression of MTA1, E-cadherin, Vimentin, Snail, PCNA, Bax and Bcl-2 in tissues and transfected cells were measured using RT-qPCR and western blot analysis. Cell proliferation, apoptosis, migration and invasion were evaluated by CCK-8, flow cytometry, scratch tests and Transwell assays. Tumor xenografts were conducted in nude mice to determine tumor growth. SPC-A-1 cells with the highest levels of miR-183 expression were selected. Compared with adjacent normal tissues, the expression of miR-183 and the mRNA and protein expression of E-cadherin and Bax were decreased in NSCLC tissues, while mRNA and protein expression of MTA1, Vimentin, snail, PCNA and Bcl-2 were increased. MiR-183 was over-expressed in the miR-183 mimic group and under-expressed in the miR-183 inhibitor and miR-183 inhibitor + siRNA-MTA1 groups. In the miR-183 mimic and siRNA-MTA1 groups, the mRNA and protein expression of E-cadherin and Bax, as well as cell apoptosis, were enhanced, while the expression levels of MTA1, Vimentin, snail, PCNA and Bcl-2 mRNA and protein, cell proliferation, migration, invasion and tumor growth were reduced relative to the blank and NC groups. The miR-183 inhibitor group exhibited an opposite trend. Our study indicates that miR-183 down-regulates MTA1 to inhibit the proliferation, EMT, migration and invasion of human NSCLC cells.

Yang CL ，Zheng XL ，Ye K ，Ge H ，Sun YN ，Lu YF ，Fan QX ... -  《-》

MicroRNA-300 promotes apoptosis and inhibits proliferation, migration, invasion and epithelial-mesenchymal transition via the Wnt/β-catenin signaling pathway by targeting CUL4B in pancreatic cancer cells.

The study aims to verify the hypothesis that up-regulation of microRNA-300 (miR-300) targeting CUL4B promotes apoptosis and suppresses proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of pancreatic cancer cells by regulating the Wnt/β-catenin signaling pathway. Pancreatic cancer tissues and adjacent tissues were collected from 110 pancreatic cancer patients. Expression of miR-300, CUL4B, Wnt, β-catenin, E-cadherin, N-cadherin, Snail, GSK-3β, and CyclinD1 were detected using qRT-PCR and Western blot. CFPAC-1, Capan-1, and PANC-1 were classified into blank, negative control (NC), miR-300 mimics, miR-300 inhibitors, siRNA-CUL4B, and miR-300 inhibitors + siRNA-CUL4B groups. The proliferation, migration, invasion abilities, the cell cycle distribution, and apoptosis rates were measured in CCK-8 and Transwell assays. Pancreatic cancer tissues showed increased CUL4B expression but decreased miR-300 expression. When miR-300 was lowly expressed, CUL4B was upregulated which in-turn activated the Wnt/β-catenin pathway to protect the β-catenin expression and thus induce EMT. When miR-300 was highly expressed, CUL4B was downregulated which in-turn inhibited the Wnt/β-catenin pathway to prevent EMT. Weakened cell migration and invasion abilities and enhanced apoptosis were observed in the CUL4B group. The miR-300 inhibitors group exhibited an evident increase in growth rate accompanied the largest tumor volume. Smaller tumor volume and slower growth rate were observed in the miR-300 mimics and siRNA-CUL4B group. Our study concludes that lowly expressed miR-300 may contribute to highly expressed CUL4B activating the Wnt/β-catenin signaling pathway and further stimulating EMT, thus promoting proliferation and migration but suppressing apoptosis of pancreatic cancer cells.

Zhang JQ ，Chen S ，Gu JN ，Zhu Y ，Zhan Q ，Cheng DF ，Chen H ，Deng XX ，Shen BY ，Peng CH ... -  《-》

MicroRNA-494 acts as a tumor suppressor in pancreatic cancer, inhibiting epithelial-mesenchymal transition, migration and invasion by binding to SDC1.

Yang Y ，Tao X ，Li CB ，Wang CM ... -  《-》

MTA1 promotes epithelial to mesenchymal transition and metastasis in non-small-cell lung cancer.

Ma K ，Fan Y ，Dong X ，Dong D ，Guo Y ，Wei X ，Ning J ，Geng Q ，Wang C ，Hu Y ，Li M ，Niu W ，Li E ，Wu Y ... -  《Oncotarget》