MicroRNA Dysregulation Associated with Red Blood Cell Storage

Chen, Xiaojie; Xie, Xuhong; Xing, Yanfen; Yang, Xiuhua; Zhang, Yuan; Wei, Yaming

doi:10.1159/000489321

Cited by 8 publications

(19 citation statements)

References 44 publications

(71 reference statements)

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“…Pontes et al reported that approximately 22% of miRNAs undergo decrease in their expression levels from day 1 to day 5, whereas other miRNAs can increase even after seven days following blood collection [18]. Interestingly, it has been reported that some miRNAs are also upregulated in red blood cells (anucleate cells) during 4°C storage [31]. It remains unclear whether the observed differential miRNA expression is universally due to degradation of miRNAs as a result of storage in all types of stored tissue specimens.…”

Section: Discussionmentioning

confidence: 99%

Cold storage conditions modify microRNA expressions for platelet transfusion

et al. 2019

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MicroRNAs (miRNAs) are small RNA molecules that modulate gene and protein expression in hematopoiesis. Platelets are known to contain a fully functional miRNA machinery. While platelets used for transfusion are normally stored at room temperature, recent evidence suggests more favorable effects under a cold-storage condition, including higher adhesion and aggregation properties. Thus, we sought to determine whether functional differences in platelets are associated with the differential profiling of platelet miRNA expressions. To obtain the miRNA expression profile, next-generation sequencing was performed on human platelets obtained from 10 healthy subjects. The miRNAs were quantified after being stored in three different conditions: 1) baseline (before storage), 2) stored at 22°C with agitation for 72 h, and 3) stored at 4°C for 72 h. Following the identification of miRNAs by sequencing, the results were validated at the level of mature miRNAs from 18 healthy subjects, by using quantitative polymerase chain reaction (qPCR). Differential expression was observed for 125 miRNAs that were stored at 4°C and 9 miRNAs stored at 22°C as compared to the baseline. The validation study by qPCR confirmed that storage at 4°C increased the expression levels (fold change 95% CI) of mir-20a-5p (1.87, p<0.0001), mir-10a-3p (1.88, p<0.0001), mir-16-2-3p (1.54, p<0.01), and mir-223-5p (1.38, p<0.05), compared with those of the samples stored at 22°C. These results show that miRNAs correlate with platelet quality under specific storage conditions. The data indicate that miRNAs could be potentially used as biomarkers of platelet quality.

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Section: Discussionmentioning

confidence: 99%

Cold storage conditions modify microRNA expressions for platelet transfusion

et al. 2019

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“…These changes in miRNA expression with holding time may be due to miRNAs released from red blood cells (RBC). MiRNAs from RBCs and exosomes of RBCs have been found to be dysregulated with holding time (Chen et al, 2018;Huang et al, 2019). Specifically, previous work profiling 52 miRNAs of RBCs have shown that hsa-miR-150-5p and hsa-miR-197-3p levels increase after prolonged blood storage (Kannan and Atreya, 2010).…”

Section: Discussionmentioning

confidence: 99%

Whole Blood Holding Time Prior to Plasma Processing Alters microRNA Expression Profile

et al. 2022

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MicroRNAs (miRNAs) can exhibit aberrant expression under different physiological and pathological conditions. Therefore, differentially expressed circulating miRNAs have been a focus of biomarker discovery research. However, the use of circulating miRNAs comes with challenges which may hinder the reliability for their clinical application. These include varied sample collection protocols, storage times/conditions, sample processing and analysis methods. This study focused on examining the effect of whole blood holding time on the stability of plasma miRNA expression profiles. Whole blood samples were collected from healthy pregnant women and were held at 4°C for 30 min, 2 h, 6 h or 24 h prior to processing for plasma isolation. Plasma RNA was extracted and the expression of 179 miRNAs were analyzed. Unsupervised principal component analysis demonstrated that whole blood holding time was a major source of variation in miRNA expression profiles with 53 of 179 miRNAs showing significant changes in expression. Levels of specific miRNAs previously reported to be associated with pregnancy-associated complications such as hsa-miR-150-5p, hsa-miR-191-5p, and hsa-miR-29a-3p, as well as commonly used endogenous miRNA controls, hsa-miR-16-5p, hsa-miR-25-3p, and hsa-miR-223-3p were significantly altered with increase in blood holding time. Current protocols for plasma-based miRNA profiling for diagnostics describe major differences in whole blood holding periods ranging from immediately after collection to 26 h after. Our results demonstrate holding time can have dramatic effects on analytical reliability and reproducibility. This highlights the importance of standardization of blood holding time prior to processing for plasma in order to minimize introduction of non-biological variance in miRNA profiles.

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“…We proceeded to identify potentially circRNA-miR-NA-mRNA regulatory axes based on our formerly identified DE-circRNAs (day20 vs. day 0) and the DE-miRNAs (day 20 vs. day 0) [3]. It is noticed that the DE-miRNAs (109 increased and 102 decreased miRNAs) were detected from healthy male RBCs, which contributes to identifying 15 DE-circRNA-DE-miRNA interactions (Table 1).…”

Section: Construction Network Of Differentially Expressed Circrnas An...mentioning

confidence: 99%

“…It is known that the precise regulation of both coding and noncoding RNAs is essential for hematopoietic stem cell differentiation to RBC. The RBC storage lesion is often accompanied by significant transcriptome changes; we previously found that 211 miRNAs were dysregulated in day 20 group compared to day 0 group [3]. As a vital participant in transcriptome changes of stored RBCs, circular RNA (circRNA) is endogenously expressed as single-stranded and always appears as a covalently closed circular molecule [4].…”

Section: Introductionmentioning

confidence: 99%

Profiling and Bioinformatics Analysis Revealing Differential Circular RNA Expression about Storage Lesion Regulatory in Stored Red Blood Cells

Zhang

Huang²,

Zhang

et al. 2021

Transfus Med Hemother

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Introduction: Circular RNA (circRNA) plays an important role in regulating metabolism of red blood cells (RBCs) and their storage lesions, but the study of how circRNA expression changes in stored RBCs has rarely been conducted. Methods: The expression change of circRNA was systemically evaluated via high-throughput sequencing on healthy RBCs on day 0, 20, and 40. And then we confirmed the reliability of the high-throughput sequencing analysis by RT-qPCR characterization on selected circRNAs. A higher parental gene enrichment was used to explore circRNA function in pathways. In addition, we deciphered a dysregulated circRNA-related ceRNAs network, and identified three circRNA-miRNA-mRNA regulatory axes related to storage lesion. Results: We identified 2,586 known and 6,216 putative novel circRNAs, more than 100 circRNAs expression levels were shifted, and the number of downregulated circRNAs was greater with longer storage time. Furthermore, a higher parental gene enrichment related to circRNA was found in pathways, including cAMP signaling pathway, ubiquitin-mediated proteolysis, apoptosis, adhesion, MAPK signaling pathway, cystine methionine metabolism, RNA degradation, RNA transport, TGF-β, and actin regulatory pathway. hsa_circ_0007127-miR-513a-5p-SMAD4, hsa_circ_0000033-miR-19a-3p-VAMP3, and hsa_circ_0005546-miR-4720-CCND3 regulatory axes related to storage lesion was found. Conclusions: Through investigation in circRNAs profile and circRNA-miRNA-mRNA interactions, this study provides insights on stored RBC circRNA expression changes, which closely relate to the storage lesion of RBCs and their physiological functions.

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MicroRNA Dysregulation Associated with Red Blood Cell Storage

Cited by 8 publications

References 44 publications

Cold storage conditions modify microRNA expressions for platelet transfusion

Cold storage conditions modify microRNA expressions for platelet transfusion

Whole Blood Holding Time Prior to Plasma Processing Alters microRNA Expression Profile

Profiling and Bioinformatics Analysis Revealing Differential Circular RNA Expression about Storage Lesion Regulatory in Stored Red Blood Cells

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