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MicroRNA expression profiling in endometrial adenocarcinoma
University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. Örebro universitet, Institutionen för hälsovetenskap och medicin.
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 [en]
Endometrial cancer, microRNA, BDII rat model, normalization, endogenous controls
National Category
Cancer and Oncology
Research subject
Medicine
Identifiers
URN: urn:nbn:se:his:diva-10886ISBN: 9789175290638 (print)OAI: oai:DiVA.org:his-10886DiVA, id: diva2:809473
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
List of papers
1. miREC: a database of miRNAs involved in the development of endometrial cancer
Open this publication in new window or tab >>miREC: a database of miRNAs involved in the development of endometrial cancer
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2015 (English)In: BMC Research Notes, E-ISSN 1756-0500, Vol. 8, no 1, article id 104Article in journal (Refereed) Published
Abstract [en]

Background

Endometrial cancer (EC) is the most frequently diagnosed gynecological malignancy and the fourth most common cancer diagnosis overall among women. As with many other forms of cancer, it has been shown that certain miRNAs are differentially expressed in EC and these miRNAs are believed to play important roles as regulators of processes involved in the development of the disease. With the rapidly growing number of studies of miRNA expression in EC, there is a need to organize the data, combine the findings from experimental studies of EC with information from various miRNA databases, and make the integrated information easily accessible for the EC research community.

Findings

The miREC database is an organized collection of data and information about miRNAs shown to be differentially expressed in EC. The database can be used to map connections between miRNAs and their target genes in order to identify specific miRNAs that are potentially important for the development of EC. The aim of the miREC database is to integrate all available information about miRNAs and target genes involved in the development of endometrial cancer, and to provide a comprehensive, up-to-date, and easily accessible source of knowledge regarding the role of miRNAs in the development of EC. Database URL: http://www.mirecdb.orgwebcite.

Conclusions

Several databases have been published that store information about all miRNA targets that have been predicted or experimentally verified to date. It would be a time-consuming task to navigate between these different data sources and literature to gather information about a specific disease, such as endometrial cancer. The miREC database is a specialized data repository that, in addition to miRNA target information, keeps track of the differential expression of genes and miRNAs potentially involved in endometrial cancer development. By providing flexible search functions it becomes easy to search for EC-associated genes and miRNAs from different starting points, such as differential expression and genomic loci (based on genomic aberrations).

Place, publisher, year, edition, pages
BioMed Central, 2015
Keywords
Endometrial cancer, MicroRNA, Database
National Category
Cancer and Oncology
Research subject
Medical sciences; Bioinformatics; Infection Biology
Identifiers
urn:nbn:se:his:diva-10891 (URN)10.1186/s13104-015-1052-9 (DOI)25889518 (PubMedID)2-s2.0-84940717539 (Scopus ID)
Note

CC BY 4.0

© 2015 Ulfenborg et al.; licensee BioMed Central. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Available from: 2015-05-05 Created: 2015-05-05 Last updated: 2024-01-17Bibliographically approved
2. Validation of Suitable Endogenous Control Genes for Quantitative PCR Analysis of microRNA gene expression in a rat model of endometrial cancer
Open this publication in new window or tab >>Validation of Suitable Endogenous Control Genes for Quantitative PCR Analysis of microRNA gene expression in a rat model of endometrial cancer
2013 (English)In: Cancer Cell International, E-ISSN 1475-2867, Vol. 13, article id 45Article in journal (Refereed) Published
Abstract [en]

Background

MicroRNAs are small RNA molecules that negatively regulate gene expression by translational inhibition or mRNA cleavage. The discovery that abnormal expression of particular miRNAs contributes to human disease, including cancer, has spurred growing interest in analysing expression profiles of these molecules. Quantitative polymerase chain reaction is frequently used for quantification of miRNA expression due to its sensitivity and specificity. To minimize experimental error in this system an appropriate endogenous control gene must be chosen. An ideal endogenous control gene should be expressed at a constant level across all samples and its expression stability should be unaffected by the experimental procedure.

Results

The expression and validation of candidate control genes (4.5S RNA(H) A, Y1, 4.5S RNA(H) B, snoRNA, U87 and U6) was examined in 21 rat cell lines to establish the most suitable endogenous control for miRNA analysis in a rat model of cancer. The stability of these genes was analysed using geNorm and NormFinder algorithms. U87 and snoRNA were identified as the most stable control genes, while Y1 was least stable.

Conclusion

This study identified the control gene that is most suitable for normalizing the miRNA expression data in rat. That reference gene will be useful when miRNAs expression are analyzed in order to find new miRNA markers for endometrial cancer in rat.

Place, publisher, year, edition, pages
BioMed Central (BMC), 2013
Keywords
Endogenous control genes, microRNA, Endometrial cancer
National Category
Natural Sciences Cancer and Oncology
Research subject
Natural sciences; Bioinformatics
Identifiers
urn:nbn:se:his:diva-8384 (URN)10.1186/1475-2867-13-45 (DOI)000319504800001 ()23680393 (PubMedID)2-s2.0-84878248686 (Scopus ID)
Note

CC BY 2.0

Available from: 2013-08-12 Created: 2013-08-09 Last updated: 2023-09-08Bibliographically approved
3. Verification of microRNA expression in human endometrial adenocarcinoma
Open this publication in new window or tab >>Verification of microRNA expression in human endometrial adenocarcinoma
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
Keywords
Endometrial adenocarcinoma, microRNA, mir-34a, Target genes
National Category
Cancer and Oncology
Research subject
Biomedical Genetics; Bioinformatics; Infection Biology
Identifiers
urn:nbn:se:his:diva-10890 (URN)10.1186/s12885-016-2296-z (DOI)000373329900001 ()27039384 (PubMedID)2-s2.0-84962003924 (Scopus ID)
Note

CC BY 4.0

Available from: 2015-05-05 Created: 2015-05-05 Last updated: 2023-09-21Bibliographically approved
4. MicroRNA expression in human endometrial adenocarcinoma
Open this publication in new window or tab >>MicroRNA expression in human endometrial adenocarcinoma
2014 (English)In: Cancer Cell International, E-ISSN 1475-2867, Vol. 14, no 1, article id 88Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: MicroRNAs are small non-coding RNAs that play crucial roles in the pathogenesis of different cancer types. The aim of this study was to identify miRNAs that are differentially expressed in endometrial adenocarcinoma compared to healthy endometrium. These miRNAs can potentially be used to develop a panel for classification and prognosis in order to better predict the progression of the disease and facilitate the choice of treatment strategy.

METHODS: Formalin fixed paraffin embedded endometrial tissue samples were collected from the Örebro university hospital. QPCR was used to quantify the expression levels of 742 miRNAs in 30 malignant and 20 normal endometrium samples. After normalization of the qPCR data, miRNAs differing significantly in expression between normal and cancer samples were identified, and hierarchical clustering analysis was used to identify groups of miRNAs with coordinated expression profiles.

RESULTS: In comparisons between endometrial adenocarcinoma and normal endometrium samples 138 miRNAs were found to be significantly differentially expressed (p < 0.001) among which 112 miRNAs have not been previous reported for endometrial adenocarcinoma.

CONCLUSION: Our study shows that several miRNAs are differentially expressed in endometrial adenocarcinoma. These identified miRNA hold great potential as target for classification and prognosis of this disease. Further analysis of the differentially expressed miRNA and their target genes will help to derive new biomarkers that can be used for classification and prognosis of endometrial adenocarcinoma.

Place, publisher, year, edition, pages
London: BioMed Central (BMC), 2014
Keywords
Endometrial adenocarcinoma, MicroRNA, Quantitative polymerase chain reaction
National Category
Cancer and Oncology
Research subject
Medical sciences; Bioinformatics; Infection Biology
Identifiers
urn:nbn:se:his:diva-10451 (URN)10.1186/s12935-014-0088-6 (DOI)000346199300001 ()25419182 (PubMedID)2-s2.0-84988672626 (Scopus ID)
Funder
Knowledge Foundation, 2009/091
Note

CC BY 4.0

© 2014 Jurcevic et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Available from: 2014-12-18 Created: 2014-12-18 Last updated: 2023-09-08Bibliographically approved

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