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Verification of microRNA expression in human endometrial adenocarcinoma
University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. (Biomedicinsk genetik, Biomedical genetics / Infektionsbiologi, Infection Biology)
University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. (Biomedicinsk genetik, Biomedical genetics)
University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. (Bioinformatik, Bioinformatics)ORCID iD: 0000-0001-6254-4335
University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. (Bioinformatik, Bioinformatics)ORCID iD: 0000-0001-8962-0860
2016 (English)In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 16, no 1, article id 261Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
BioMed Central (BMC), 2016. Vol. 16, no 1, article id 261
Keywords [en]
Endometrial adenocarcinoma, microRNA, mir-34a, Target genes
National Category
Cancer and Oncology
Research subject
Biomedical Genetics; Bioinformatics; Infection Biology
Identifiers
URN: urn:nbn:se:his:diva-10890DOI: 10.1186/s12885-016-2296-zISI: 000373329900001PubMedID: 27039384Scopus ID: 2-s2.0-84962003924OAI: oai:DiVA.org:his-10890DiVA, id: diva2:810722
Note

CC BY 4.0

Available from: 2015-05-05 Created: 2015-05-05 Last updated: 2023-09-21Bibliographically approved
In thesis
1. MicroRNA expression profiling in endometrial adenocarcinoma
Open this publication in new window or tab >>MicroRNA expression profiling in endometrial adenocarcinoma
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Place, publisher, year, edition, pages
Örebro: Örebro university, 2015. p. 53
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 118
Keywords
Endometrial cancer, microRNA, BDII rat model, normalization, endogenous controls
National Category
Cancer and Oncology
Research subject
Medicine
Identifiers
urn:nbn:se:his:diva-10886 (URN)9789175290638 (ISBN)
Public defence
2015-03-27, Portalen, Högskolan i Skövde, Högskolevägen, 09:00 (English)
Opponent
Supervisors
Available from: 2015-05-04 Created: 2015-05-04 Last updated: 2023-05-02Bibliographically approved

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Jurcevic, SanjaKlinga-Levan, KarinOlsson, BjörnEjeskär, Katarina

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