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Titel: Deregulated microRNA and mRNA expression profiles in the peripheral blood of patients with Marfan syndrome
VerfasserIn: Abu-Halima, Masood
Kahraman, Mustafa
Henn, Dominic
Rädle-Hurst, Tanja
Keller, Andreas
Abdul-Khaliq, Hashim
Meese, Eckart
Sprache: Englisch
Titel: Journal of Translational Medicine
Bandnummer: 16
Heft: 1
Verlag/Plattform: BMC
Erscheinungsjahr: 2018
Freie Schlagwörter: MicroRNA
mRNA
Integration analysis
Marfan syndrome
Fibrillin
DDC-Sachgruppe: 610 Medizin, Gesundheit
Dokumenttyp: Journalartikel / Zeitschriftenartikel
Abstract: Background MicroRNAs (miRNAs) are small RNAs regulating gene expression post-transcriptionally. While acquired changes of miRNA and mRNA profiles in cancer have been extensively studied, little is known about expression changes of circulating miRNAs and messenger RNAs (mRNA) in monogenic constitutional anomalies affecting several organ systems, like Marfan syndrome (MFS). We performed integrated miRNA and mRNA expression profiling in blood samples of Marfan patients in order to investigate deregulated miRNA and mRNA networks in these patients which could serve as potential diagnostic and prognostic tools for MFS therapy. Methods MiRNA and mRNA expression profiles were determined in blood samples from MFS patients (n = 7) and from healthy volunteer controls (n = 7) by microarray analysis. Enrichment analyses of altered mRNA expression were identified using bioinformatic tools. Results A total of 28 miRNAs and 32 mRNAs were found to be significantly altered in MFS patients compared to controls (> 2.0-fold change, adjusted P < 0.05). The expression of 11 miRNA and 6 mRNA candidates was validated by RT-qPCR in an independent cohort of 26 MFS patients and 26 matched HV controls. Significant inverse correlations were evident between 8 miRNAs and 5 mRNAs involved in vascular pathology, inflammation and telomerase regulation. Significant positive correlations were present for 7 miRNAs with age, for 2 miRNAs with the MFS aortic root status (Z-score) and for 7 miRNAs with left ventricular end-diastolic diameter in MFS patients. In addition, miR-331-3p was significantly up-regulated in MFS patients without mitral valve prolapse (MVP) as compared with patients with MVP. Conclusions Our data show deregulated gene and miRNA expression profiles in the peripheral blood of MFS patients, demonstrating several candidates for prognostic biomarkers for cardiovascular manifestations in MFS as well as targets for novel therapeutic approaches. A deregulation of miRNA expression seems to play an important role in MFS, highlighting the plethora of effects on post-transcriptional regulation of miRNAs and mRNAs initiated by constitutional mutations in single genes.
DOI der Erstveröffentlichung: 10.1186/s12967-018-1429-3
Link zu diesem Datensatz: urn:nbn:de:bsz:291--ds-353431
hdl:20.500.11880/32242
http://dx.doi.org/10.22028/D291-35343
ISSN: 1479-5876
Datum des Eintrags: 26-Jan-2022
Bezeichnung des in Beziehung stehenden Objekts: Additional files
In Beziehung stehendes Objekt: https://static-content.springer.com/esm/art%3A10.1186%2Fs12967-018-1429-3/MediaObjects/12967_2018_1429_MOESM1_ESM.pptx
https://static-content.springer.com/esm/art%3A10.1186%2Fs12967-018-1429-3/MediaObjects/12967_2018_1429_MOESM2_ESM.pptx
https://static-content.springer.com/esm/art%3A10.1186%2Fs12967-018-1429-3/MediaObjects/12967_2018_1429_MOESM3_ESM.docx
Fakultät: M - Medizinische Fakultät
Fachrichtung: M - Humangenetik
M - Medizinische Biometrie, Epidemiologie und medizinische Informatik
M - Pädiatrie
Professur: M - Prof. Dr. Hashim Abdul-Khaliq
M - Univ.-Prof. Dr. Andreas Keller
M - Prof. Dr. Eckhart Meese
M - Prof. Dr. Tanja Rädle-Hurst
Sammlung:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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