The use of high-throughput small RNA sequencing is well established as a technique to unveil the miRNAs in various tissues. The miRNA profiles are different between infected and non-infected tissues. We compare the SARS-CoV-2 positive and SARS-CoV-2 negative RNA samples extracted from human nasopharynx tissue samples to show different miRNA profiles. We explored differentially expressed miRNAs in response to SARS-CoV-2 in the RNA extracted from nasopharynx tissues of 10 SARS-CoV-2-positive and 10 SARS-CoV-2-negative patients. miRNAs were identified by small RNA sequencing, and the expression levels of selected miRNAs were validated by real-time RT-PCR. We identified 943 conserved miRNAs, likely generated through posttranscriptional modifications. The identified miRNAs were expressed in both RNA groups, NegS and PosS: miR-148a, miR-21, miR-34c, miR-34b, and miR-342. The most differentially expressed miRNA was miR-21, which is likely closely linked to the presence of SARS-CoV-2 in nasopharynx tissues. Our results contribute to further understanding the role of miRNAs in SARS-CoV-2 pathogenesis, which may be crucial for understanding disease symptom development in humans.

• Klíčová slova
• SARS-CoV-2, miRNAs, mir-21, real-time RT-PCR, small RNA sequencing,
• MeSH
• analýza hlavních komponent MeSH
• COVID-19 patologie   virologie   MeSH
• down regulace MeSH
• kvantitativní polymerázová řetězová reakce MeSH
• lidé MeSH
• mikro RNA chemie   metabolismus   MeSH
• nazofarynx metabolismus   virologie   MeSH
• RNA virová metabolismus   MeSH
• SARS-CoV-2 genetika   izolace a purifikace   fyziologie   MeSH
• sekvenční analýza RNA MeSH
• transkriptom MeSH
• upregulace MeSH
• vysoce účinné nukleotidové sekvenování MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• mikro RNA MeSH
• RNA virová MeSH

Hematopoiesis, the formation of blood cells from hematopoietic stem cells (HSC), is a highly regulated process. Since the discovery of microRNAs (miRNAs), several studies have shown their significant role in the regulation of the hematopoietic system. Impaired expression of miRNAs leads to disrupted cellular pathways and in particular causes loss of hematopoietic ability. Here, we report a previously unrecognized function of miR-143 in granulopoiesis. Hematopoietic cells undergoing granulocytic differentiation exhibited increased miR-143 expression. Overexpression or ablation of miR-143 expression resulted in accelerated granulocytic differentiation or block of differentiation, respectively. The absence of miR-143 in mice resulted in a reduced number of mature granulocytes in blood and bone marrow. Additionally, we observed an association of high miR-143 expression levels with a higher probability of survival in two different cohorts of patients with acute myeloid leukemia (AML). Overexpression of miR-143 in AML cells impaired cell growth, partially induced differentiation, and caused apoptosis. Argonaute2-RNA-Immunoprecipitation assay revealed ERK5, a member of the MAPK-family, as a target of miR-143 in myeloid cells. Further, we observed an inverse correlation of miR-143 and ERK5 in primary AML patient samples, and in CD34+ HSPCs undergoing granulocytic differentiation and we confirmed functional relevance of ERK5 in myeloid cells. In conclusion, our data describe miR-143 as a relevant factor in granulocyte differentiation, whose expression may be useful as a prognostic and therapeutic factor in AML therapy.

• MeSH
• 3' nepřekládaná oblast MeSH
• akutní myeloidní leukemie metabolismus   mortalita   patologie   MeSH
• antagomiry metabolismus   MeSH
• apoptóza MeSH
• buněčná diferenciace MeSH
• granulocyty cytologie   metabolismus   MeSH
• hematopoetické kmenové buňky cytologie   metabolismus   MeSH
• lidé MeSH
• mikro RNA antagonisté a inhibitory   genetika   metabolismus   MeSH
• míra přežití MeSH
• mitogenem aktivovaná proteinkinasa 7 chemie   genetika   metabolismus   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• prognóza MeSH
• proliferace buněk MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 3' nepřekládaná oblast MeSH
• antagomiry MeSH
• MAPK7 protein, human MeSH Prohlížeč
• mikro RNA MeSH
• MIRN143 microRNA, human MeSH Prohlížeč
• mitogenem aktivovaná proteinkinasa 7 MeSH

The aim of the study was to demonstrate that preterm birth (PTB) is associated with altered C19MC microRNA expression profile in placental tissues. Gene expression of 15 placental specific microRNAs (miR‑512‑5p, miR‑515‑5p, miR‑516‑5p, miR‑517‑5p, miR‑518b, miR‑518f‑5p, miR‑519a, miR‑519d, miR‑519e‑5p, miR‑520a‑5p, miR‑520h, miR‑524‑5p, miR‑525‑5p, miR‑526a and miR‑526b‑5p) was compared between groups: 34 spontaneous PTB, 108 preterm prelabor rupture of membranes (PPROM) and 20 term in labor pregnancies. Correlation between variables including relative microRNA quantification in placental tissues and the gestational age at delivery, white blood cell (WBC) count at admission and serum levels of C‑reactive protein at admission in patients with PPROM and PTB was determined. Expression profile of microRNAs was different between PPROM and term in labor pregnancies, PTB and term in labor pregnancies, and between gestational age‑matched PPROM and PTB groups. When compared with term in labor pregnancies, while C19MC microRNAs showed a downregulation in PPROM pregnancies (miR‑525‑5p), in PTB pregnancies C19MC microRNAs were upregulated (miR‑515‑5p, miR‑516‑5p, miR‑518b, miR‑518f‑5p, miR‑519a, miR‑519e‑5p, miR‑520a‑5p, miR‑520h, and miR‑526b‑5p) or showed a trend to upregulation (miR‑519d and miR‑526a). In comparison to PTB pregnancies, the PPROM group demonstrated a significant portion of downregulated C19MC microRNAs (miR‑516‑5p, miR‑517‑5p, miR‑518b, miR‑518f‑5p, miR‑519a, miR‑519d, miR‑519e‑5p, miR‑520a‑5p, miR‑520h, miR‑525‑5p, miR‑526a and miR‑526b‑5p). In the group of PPROM pregnancies, a weak negative correlation between the gestational age at delivery and microRNA gene expression in placental tissue for all examined C19MC microRNAs was observed. PTB pregnancies showed a positive correlation (miR‑512‑5p, miR‑515‑5p, miR‑519e‑5p) or a trend to positive correlation (miR‑516‑5p, miR‑518b, miR‑520h) between particular C19MC microRNAs and maternal WBC count at admission. Our study demonstrates that upregulation of C19MC microRNAs is a characteristic phenomenon of PTB. PPROM pregnancies have a tendency to produce lower levels of miR‑525‑5p. All examined C19MC microRNAs displayed decreased expression with advancing gestational age in PPROM group.

• MeSH
• C-reaktivní protein metabolismus   MeSH
• dospělí MeSH
• down regulace genetika   MeSH
• gestační stáří MeSH
• lidé MeSH
• mikro RNA genetika   metabolismus   MeSH
• multigenová rodina * MeSH
• novorozenec MeSH
• placenta metabolismus   MeSH
• porodní děj * MeSH
• předčasný odtok plodové vody krev   genetika   MeSH
• předčasný porod krev   genetika   MeSH
• stanovení celkové genové exprese * MeSH
• těhotenství MeSH
• upregulace genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• novorozenec MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• C-reaktivní protein MeSH
• mikro RNA MeSH

OBJECTIVES: A nested case control study of a longitudinal cohort comparing pregnant women enrolled at 10 to 13 gestational weeks was carried out to evaluate risk assessment for preeclampsia and IUGR based on circulating placental specific C19MC microRNAs in early pregnancy. METHODS: The expression of placental specific C19MC microRNAs (miR-516b-5p, miR-517-5p, miR-518b, miR-520a-5p, miR-520h, and miR-525-5p) was determined in plasma samples from pregnancies that subsequently developed preeclampsia (n = 21), IUGR (n = 18), and 58 normal pregnancies using real-time PCR and comparative Ct method relative to synthetic Caenorhabditis elegans microRNA (cel-miR-39). RESULTS: Circulating C19MC microRNAs were up-regulated (miR-517-5p, p = 0.005; miR-518b, p = 0.013; miR-520h, p = 0.021) or showed a trend toward up-regulation in patients destined to develop preeclampsia (miR-520a-5p, p = 0.067; miR-525-5p, p = 0.073). MiR-517-5p had the best predictive performance for preeclampsia with a sensitivity of 42.9%, a specificity of 86.2%, a PPV of 52.9% and a NPV of 80.6%. The combination of all examined circulating C19MC microRNAs had no advantage over using only the miR-517-5p biomarker to predict the occurrence of preeclampsia (a sensitivity of 20.6%, a specificity of 90.8%, a PPV of 44.8%, and a NPV of 76.0%). CONCLUSIONS: Up-regulation of miR-517-5p, miR-518b and miR-520h was associated with a risk of later development of preeclampsia. First trimester screening of extracellular miR-517-5p identified a proportion of women with subsequent preeclampsia. No circulating C19MC microRNA biomarkers were identified that could predict later occurrence of IUGR.

• MeSH
• biologické markery krev   MeSH
• dospělí MeSH
• lidé MeSH
• mikro RNA krev   MeSH
• prediktivní hodnota testů MeSH
• preeklampsie krev   diagnóza   MeSH
• prenatální diagnóza metody   MeSH
• první trimestr těhotenství krev   MeSH
• růstová retardace plodu krev   diagnóza   MeSH
• stanovení celkové genové exprese MeSH
• studie případů a kontrol MeSH
• těhotenství MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• biologické markery MeSH
• mikro RNA MeSH