| Experiment ID | EXP00175 |
| Reference | Title: Lack of microRNA-101 causes E-cadherin functional deregulation through EZH2up-regulation in intestinal gastric cancer. Author: Carvalho J, van Grieken NC, Pereira PM, Sousa S, Tijssen M, Buffart TE,Diosdado B, Grabsch H, Santos MA, Meijer G, Seruca R, Carvalho B, Oliveira C. Journal: J Pathol. 2012 Sep;228(1):31-44. doi: 10.1002/path.4032. Epub 2012 May 23. Abstract: E-cadherin expression disruption is commonly observed in metastatic epithelialcancers and is a crucial step in gastric cancer (GC) initiation and progression. As aberrant expression of microRNAs often perturb the normal expression/function of pivotal cancer-related genes, we characterized and dissected a pathway thatcauses E-cadherin dysfunction via loss of microRNA-101 and up-regulation of EZH2 expression in GC. MicroRNA microarray expression profiling and array-CGH wereused to reinforce miR-101 involvement in GC. By using quantitative real-time PCR and quantitative SNaPshot genomic PCR, we confirmed that miR-101 wassignificantly down-regulated in GC (p < 0.0089) in comparison with normal gastricmucosas and, at least in 65% of the GC cases analysed, this down-regulation wascaused by deletions and/or microdeletions at miR-101 genomic loci. Moreover,around 40% of cases showing miR-101 down-regulation displayed concomitant EZH2over-expression (at the RNA and protein levels), which, in turn, was associatedwith loss/aberrant expression of E-cadherin. Interestingly, this occurredpreferentially in intestinal-type GCs, retaining allele(s) untargeted byclassical CDH1-inactivating mechanisms. We also demonstrated that miR-101 gain offunction or direct inhibition of EZH2 in Kato III GC cells led to a strongdepletion of endogenous EZH2 and consequent rescue of E-cadherin membranouslocalization, mimicking results obtained in clinical GC samples. In conclusion,we show that deletions and/or microdeletions at both miR-101 genomic loci causemature miR-101 down-regulation, subsequent EZH2 over-expression and E-cadherindysfunction, specifically in intestinal-type GC. PMID: 22450781 |
| Expressiion Profile | Description: Lack of microRNA-101 causes E-cadherin expression and function deregulation through EZH2 up-regulation in gastric cancer Organism: Homo sapiens GEO ID: GSE33743 Platform: GPL14895 Number of samples: 41 |
| Design and Sample | Cancer Type: gastric cancer Cancer SubType: N/D Cell Line: N/D Experimental Design: cancer vs normal Case Sample: gastric cancer Control Sample: gastric mucosas Num of Case: 37 Num of Control: 2 Quantification Software: Limma Num of miRNAs: 702 |
| Identification | Num of Up: 54 Num of Down: 58 |