miRNAs Differentially Expressed by Next-Generation Sequencing in Cord Blood Buffy Coat Samples of Boys and Girls

Lizarraga, Daneida; Huen, Karen; Combs, Mary; Escudero-Fung, Maria; Eskenazi, Brenda; Holland, Nina

doi:10.2217/epi-2016-0031

Cited by 17 publications

(20 citation statements)

References 97 publications

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“…This is substantially higher than results reported for high throughput qRT-PCR profiling platforms studies of adult plasma [9], and is one of the potential advantages of using an RNA-seq based approach to obtain genome-wide coverage. Lizarraga et al [54] used an EdgeSeq miRNA Whole Transcriptome Assay to profile the miRNAs in buffy coat of cord blood samples from 89 newborns, of which 564 miRNAs were retained for further analysis after filtering. Looney et al [26] used micorarray profiling of umbilical cord blood of 24 infants retaining 259 miR-NAs for differential expression analysis after filtering [26].…”

Section: Resultsmentioning

confidence: 99%

“…In order to develop reliable biomarkers from umbilical cord plasma, it is important that we gain perspective on the naturally occurring miRNA profiles. Previous studies have used microarrays to profile miRNAs in cord blood from neonates with HIE [26], or used RNA-seq to profile miRNA expression from trios of samples from newborn babies and their parents [51], umbilical cord blood derived cells [52,53], and cord blood buffy coat layers [54], However, a reference dataset of total miRNA profiles and miRNA editing analysis of healthy umbilical cord plasma has yet to be established.…”

Section: Introductionmentioning

confidence: 99%

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RNA-sequencing analysis of umbilical cord plasma microRNAs from healthy newborns

et al. 2018

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MicroRNAs are a class of small non-coding RNA that regulate gene expression at a posttranscriptional level. MicroRNAs have been identified in various body fluids under normal conditions and their stability as well as their dysregulation in disease has led to ongoing interest in their diagnostic and prognostic potential. Circulating microRNAs may be valuable predictors of early-life complications such as birth asphyxia or neonatal seizures but there are relatively few data on microRNA content in plasma from healthy babies. Here we performed small RNA-sequencing analysis of plasma processed from umbilical cord blood in a set of healthy newborns. MicroRNA levels in umbilical cord plasma of four male and four female healthy babies, from two different centres were profiled. A total of 1,004 individual microRNAs were identified, which ranged from 426 to 659 per sample, of which 269 microRNAs were common to all eight samples. Many of these microRNAs are highly expressed and consistent with previous studies using other high throughput platforms. While overall microRNA expression did not differ between male and female cord blood plasma, we did detect differentially edited microRNAs in female plasma compared to male. Of note, and consistent with other studies of this type, adenylation and uridylation were the two most prominent forms of editing. Six microRNAs, miR-128-3p, miR-29a-3p, miR-9-5p, miR-218-5p, 204-5p and miR-132-3p were consistently both uridylated and adenylated in female cord blood plasma. These results provide a benchmark for micro-RNA profiling and biomarker discovery using umbilical cord plasma and can be used as comparative data for future biomarker profiles from complicated births or those with earlylife developmental disorders.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

RNA-sequencing analysis of umbilical cord plasma microRNAs from healthy newborns

et al. 2018

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“…To determine the concentration of 2,083 known miRNAs in plasma from patients in our screening panel, we applied HTG EdgeSeq technology (HTG Molecular Diagnostics, Inc., Tucson, AZ), a new next-generation sequencing-based miRNA profiling platform (16,17). Fifteen-microliter aliquots of plasma from 71 patients were submitted to HTG Molecular Diagnostics for analysis.…”

Section: Mirna Expression Profiling In the Screening Panelmentioning

confidence: 99%

Circulating miRNA Profiles Associated With Hyperglycemia in Patients With Type 1 Diabetes

et al. 2018

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We investigated plasma microRNA (miRNA) profiles associated with variation of hyperglycemia, measured as hemoglobin A (HbA), in two panels of patients with type 1 diabetes (T1D). Using the HTG Molecular Diagnostics EdgeSeq platform, 2,083 miRNAs were measured in plasma from 71 patients included in a screening panel. Quantitative real-time PCR was used to measure the candidate miRNAs in plasma from 95 patients included in an independent replication panel. We found 10 miRNAs replicated in both panels and 4 with high statistical significance. The strongest positive correlations with HbA were found with miR-125b-5p ( = 0.40, = 6.0 × 10) and miR-365a-3p ( = 0.35, = 5.9 × 10). The strongest negative correlations were found with miR-5190 ( = -0.30, = 0.003) and miR-770-5p ( = -0.27, = 0.008). Pathway analysis revealed that 50 Kyoto Encyclopedia of Genes and Genomes pathways were significantly enriched by genes targeted by these four miRNAs. The axon guidance signaling pathway was enriched ( < 1 × 10) by genes targeted by all four miRNAs. In addition, three other pathways (Rap1 signaling, focal adhesion, and neurotrophin signaling) were also significantly enriched but with genes targeted by only by three of the identified miRNAs. In conclusion, our study identified four circulating miRNAs that were influenced by variation in hyperglycemia. Dysregulation of these miRNAs, which are associated with hyperglycemia in patients with T1D, may contribute to the development of diabetes complications. However, there are multitudes of possible mechanisms/pathways through which dysregulation of these miRNAs may impact risk of diabetes complications.

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“…While respective markers or marker patterns are developed, also the general tissue distribution and stability of miRNAs is explored [2,15,37,38]. Also confounding factors for miRNA profiles have been reported, including gender, age, smoking behaviour, body mass index, fitness condition, and others [16,[39][40][41][42]. However, seasonal differences of miRNA expression profiles may also have an impact miR-106b-5p let-7c-5p…”

Section: Discussionmentioning

confidence: 99%

Spring is in the air: seasonal profiles indicate vernal change of miRNA activity

et al. 2019

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The envisioned application of miRNAs as diagnostic or prognostic biomarkers calls for an in-depth understanding of their distribution and variability in different physiological states. While effects with respect to ethnic origin, age, or gender are known, the inter-individual variability of miRNAs across the four seasons remained largely hidden. We sequentially profiled the complete repertoire of blood-borne miRNAs for 25 physiologically normal individuals in spring, summer, fall, and winter (altogether 95 samples) and validated the results on 292 individuals (919 samples collected with the Mitra home sampling device) by RT-qPCR. Principal variance component analysis suggests that the largest variability observed in miRNA expression is due to individual variability and the individuals' gender. But the results also highlight a deviation of miRNA activity in samples collected during spring time. Following adjustment for multiple testing, remarkable differences are observed between spring and fall (77 miRNAs). The two most dys-regulated miRNAs were miR-181c-5p and miR-106b-5p (adjusted p-value of 0.007). Other significant miRNAs include miR-140-3p, miR-21-3p, and let-7c-5p. The dys-regulation was validated by RT-qPCR. Systems biology analysis further provides strong evidence for the immunological origin of the signals: dys-regulated miRNAs are enriched in CD56 cells and belong to various signalling and immunesystem-related pathways. Our data suggest that besides known confounding factors such as age and sex, also the season in which a test is conducted might have a considerable influence on the expression of blood-borne miRNAs and subsequently might interfere with diagnosis based on such signatures.

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miRNAs Differentially Expressed by Next-Generation Sequencing in Cord Blood Buffy Coat Samples of Boys and Girls

Cited by 17 publications

References 97 publications

RNA-sequencing analysis of umbilical cord plasma microRNAs from healthy newborns

RNA-sequencing analysis of umbilical cord plasma microRNAs from healthy newborns

Circulating miRNA Profiles Associated With Hyperglycemia in Patients With Type 1 Diabetes

Spring is in the air: seasonal profiles indicate vernal change of miRNA activity

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