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.

• Keywords
• SARS-CoV-2, miRNAs, mir-21, real-time RT-PCR, small RNA sequencing,
• MeSH
• Principal Component Analysis MeSH
• COVID-19 pathology   virology   MeSH
• Down-Regulation MeSH
• Real-Time Polymerase Chain Reaction MeSH
• Humans MeSH
• MicroRNAs chemistry   metabolism   MeSH
• Nasopharynx metabolism   virology   MeSH
• RNA, Viral metabolism   MeSH
• SARS-CoV-2 genetics   isolation & purification   physiology   MeSH
• Sequence Analysis, RNA MeSH
• Transcriptome MeSH
• Up-Regulation MeSH
• High-Throughput Nucleotide Sequencing MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• MicroRNAs MeSH
• RNA, Viral 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' Untranslated Regions MeSH
• Leukemia, Myeloid, Acute metabolism   mortality   pathology   MeSH
• Antagomirs metabolism   MeSH
• Apoptosis MeSH
• Cell Differentiation MeSH
• Granulocytes cytology   metabolism   MeSH
• Hematopoietic Stem Cells cytology   metabolism   MeSH
• Humans MeSH
• MicroRNAs antagonists & inhibitors   genetics   metabolism   MeSH
• Survival Rate MeSH
• Mitogen-Activated Protein Kinase 7 chemistry   genetics   metabolism   MeSH
• Mice, Inbred C57BL MeSH
• Mice MeSH
• Prognosis MeSH
• Cell Proliferation MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• 3' Untranslated Regions MeSH
• Antagomirs MeSH
• MAPK7 protein, human MeSH Browser
• MicroRNAs MeSH
• MIRN143 microRNA, human MeSH Browser
• Mitogen-Activated Protein Kinase 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-Reactive Protein metabolism   MeSH
• Adult MeSH
• Down-Regulation genetics   MeSH
• Gestational Age MeSH
• Humans MeSH
• MicroRNAs genetics   metabolism   MeSH
• Multigene Family * MeSH
• Infant, Newborn MeSH
• Placenta metabolism   MeSH
• Labor, Obstetric * MeSH
• Fetal Membranes, Premature Rupture blood   genetics   MeSH
• Premature Birth blood   genetics   MeSH
• Gene Expression Profiling * MeSH
• Pregnancy MeSH
• Up-Regulation genetics   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Infant, Newborn MeSH
• Pregnancy MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• C-Reactive Protein MeSH
• MicroRNAs 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
• Biomarkers blood   MeSH
• Adult MeSH
• Humans MeSH
• MicroRNAs blood   MeSH
• Predictive Value of Tests MeSH
• Pre-Eclampsia blood   diagnosis   MeSH
• Prenatal Diagnosis methods   MeSH
• Pregnancy Trimester, First blood   MeSH
• Fetal Growth Retardation blood   diagnosis   MeSH
• Gene Expression Profiling MeSH
• Case-Control Studies MeSH
• Pregnancy MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Pregnancy MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Biomarkers MeSH
• MicroRNAs MeSH