title: Verification of microRNA expression in human endometrial adenocarcinoma.
abstract: BACKGROUND
  MicroRNAs are small non-coding RNAs that have been implicated in tumor initiation and progression. In a previous study we identified 138 miRNAs as differentially expressed in endometrial adenocarcinoma compared to normal tissues. One of these miRNAs was miRNA-34a, which regulates several genes involved in the Notch pathway, which is frequently altered in endometrial cancer. The aims of this study were to verify the differential expression of a subset of miRNAs and to scrutinize the regulatory role of mir-34a on the target genes NOTCH1 and DLL1.
  
  
  METHODS
  Twenty-five miRNAs that were previously identified as differentially expressed were subjected to further analysis using qPCR. To investigate the regulation of NOTCH1 and DLL1 by mir-34a, we designed gain- and loss-of-function experiments in Ishikawa and HEK293 cell lines by transfection with a synthetic mir-34a mimic and a mir-34a inhibitor.
  
  
  RESULTS
  Of the 25 validated miRNAs, seven were down-regulated and 18 were up-regulated compared to normal endometrium, which was fully consistent with our previous findings. In addition, the up-regulation of mir-34a led to a significant decrease in mRNA levels of NOTCH1 and DLL1, while down-regulation led to a significant increase in mRNA levels of these two genes.
  
  
  CONCLUSIONS
  We verified both up-regulated and down-regulated miRNAs in the tumor samples, indicating various roles of microRNAs during tumor development. Mir-34a functions as a regulator by decreasing the expression of NOTCH1 and DLL1. Our study is the first to identify a correlation between mir-34a and its target genes NOTCH1 and DLL1 in endometrial adenocarcinoma.
authors.affiliation: Systems Biology Research Centre - Biomedical genetics, School of Bioscience, University of Skövde, Skövde, Sweden.
authors.forename: Sanja
authors.initials: S
authors.lastname: Jurcevic
authors.affiliation: Systems Biology Research Centre - Biomedical genetics, School of Bioscience, University of Skövde, Skövde, Sweden.
authors.forename: Karin
authors.initials: K
authors.lastname: Klinga-Levan
authors.affiliation: Systems Biology Research Centre - Bioinformatics, School of Bioscience, University of Skövde, Skövde, Sweden.
authors.forename: Björn
authors.initials: B
authors.lastname: Olsson
authors.affiliation: Systems Biology Research Centre - Biomedical genetics, School of Bioscience, University of Skövde, Skövde, Sweden. katarina.ejeskar@his.se.
authors.forename: Katarina
authors.initials: K
authors.lastname: Ejeskär
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000096:biosynthesis* / Q000235:genetics; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D051881:Receptor, Notch1 / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C522425:MIRN34 microRNA, human; D008565:Membrane Proteins; D035683:MicroRNAs; C497761:NOTCH1 protein, human; D012333:RNA, Messenger; D051881:Receptor, Notch1; C064045:delta protein
keywords: Endometrial adenocarcinoma; Target genes; microRNA; mir-34a