Next Article in Journal
The Brain–Skin Connection and the Pathogenesis of Psoriasis: A Review with a Focus on the Serotonergic System
Previous Article in Journal
The Diagnostic Value of Mir-133a in ST Elevation and Non-ST Elevation Myocardial Infarction: A Meta-Analysis
Previous Article in Special Issue
Therapeutic Advances of Stem Cell-Derived Extracellular Vesicles in Regenerative Medicine

This is an early access version, the complete PDF, HTML, and XML versions will be available soon.

Open AccessArticle

Circulating Small Noncoding RNAs Have Specific Expression Patterns in Plasma and Extracellular Vesicles in Myelodysplastic Syndromes and Are Predictive of Patient Outcome

1
Institute of Hematology and Blood Transfusion, U Nemocnice 1, 128 20 Prague, Czech Republic
2
Faculty of Science, Charles University, Albertov 2038, 128 00 Prague, Czech Republic
3
Czech Technical University, Karlovo namesti 13, 121 35 Prague, Czech Republic
4
First Faculty of Medicine, Charles University, Kateřinská 1660/32, 121 08 Prague, Czech Republic
5
General University Hospital, U Nemocnice 499/2, 128 08 Prague, Czech Republic
*
Author to whom correspondence should be addressed.
Cells 2020, 9(4), 794; https://doi.org/10.3390/cells9040794 (registering DOI)
Received: 30 December 2019 / Revised: 20 March 2020 / Accepted: 25 March 2020 / Published: 26 March 2020
Myelodysplastic syndromes (MDS) are hematopoietic stem cell disorders with large heterogeneity at the clinical and molecular levels. As diagnostic procedures shift from bone marrow biopsies towards less invasive techniques, circulating small noncoding RNAs (sncRNAs) have become of particular interest as potential novel noninvasive biomarkers of the disease. We aimed to characterize the expression profiles of circulating sncRNAs of MDS patients and to search for specific RNAs applicable as potential biomarkers. We performed small RNA-seq in paired samples of total plasma and plasma-derived extracellular vesicles (EVs) obtained from 42 patients and 17 healthy controls and analyzed the data with respect to the stage of the disease, patient survival, response to azacitidine, mutational status, and RNA editing. Significantly higher amounts of RNA material and a striking imbalance in RNA content between plasma and EVs (more than 400 significantly deregulated sncRNAs) were found in MDS patients compared to healthy controls. Moreover, the RNA content of EV cargo was more homogeneous than that of total plasma, and different RNAs were deregulated in these two types of material. Differential expression analyses identified that many hematopoiesis-related miRNAs (e.g., miR-34a, miR-125a, and miR-150) were significantly increased in MDS and that miRNAs clustered on 14q32 were specifically increased in early MDS. Only low numbers of circulating sncRNAs were significantly associated with somatic mutations in the SF3B1 or DNMT3A genes. Survival analysis defined a signature of four sncRNAs (miR-1237-3p, U33, hsa_piR_019420, and miR-548av-5p measured in EVs) as the most significantly associated with overall survival (HR = 5.866, p < 0.001). In total plasma, we identified five circulating miRNAs (miR-423-5p, miR-126-3p, miR-151a-3p, miR-125a-5p, and miR-199a-3p) whose combined expression levels could predict the response to azacitidine treatment. In conclusion, our data demonstrate that circulating sncRNAs show specific patterns in MDS and that their expression changes during disease progression, providing a rationale for the potential clinical usefulness of circulating sncRNAs in MDS prognosis. However, monitoring sncRNA levels in total plasma or in the EV fraction does not reflect one another, instead, they seem to represent distinctive snapshots of the disease and the data should be interpreted circumspectly with respect to the type of material analyzed.
Keywords: myelodysplastic syndromes; circulating small noncoding RNAs; extracellular vesicles; biomarkers myelodysplastic syndromes; circulating small noncoding RNAs; extracellular vesicles; biomarkers
MDPI and ACS Style

Hrustincova, A.; Krejcik, Z.; Kundrat, D.; Szikszai, K.; Belickova, M.; Pecherkova, P.; Klema, J.; Vesela, J.; Hruba, M.; Cermak, J.; Hrdinova, T.; Krijt, M.; Valka, J.; Jonasova, A.; Merkerova, M.D. Circulating Small Noncoding RNAs Have Specific Expression Patterns in Plasma and Extracellular Vesicles in Myelodysplastic Syndromes and Are Predictive of Patient Outcome. Cells 2020, 9, 794.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop