Plasma microRNA-451 as a novel hemolytic marker for β0-thalassemia/HbE disease

Leecharoenkiat, Kamonlak; Tanaka, Yuka; Harada, Yasuko; Chaichompoo, Pornthip; Sarakul, Orawan; Abe, Yasunobu; Smith, Duncan R.; Fucharoen, Suthat; Svasti, Saovaros; Umemura, Tomonari

doi:10.3892/mmr.2017.6326

Cited by 23 publications

(17 citation statements)

References 34 publications

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“…The role of miRNA genes in normal erythropoiesis [25,26] and globin expression has been demonstrated [19–21,27,28]. Therefore, the goal of the present study was to define novel miRNA genes differentially expressed in persons with SCD and contrasting high and low HbF levels.…”

Section: Resultsmentioning

confidence: 98%

MIR-144-mediated NRF2 gene silencing inhibits fetal hemoglobin expression in sickle cell disease

Zhu

Ward

et al. 2019

Experimental Hematology

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Inherited genetic modifiers and pharmacologic agents that enhance fetal hemoglobin (HbF) expression reverse the clinical severity of sickle cell disease (SCD). Recent efforts to develop novel strategies of HbF induction include discovery of molecular targets that regulate γ-globin gene transcription and translation. The purpose of this study was to perform genome-wide microRNA (miRNA) analysis to identify genes associated with HbF expression in patients with SCD. We isolated RNA from purified reticulocytes for microarray-based miRNA expression profiling. Using samples from patients with contrasting HbF levels, we observed an eightfold upregulation of miR-144–3p (miR-144) and miR-144–5p in the low-HbF group compared with those with high HbF. Additional analysis by reverse transcription quantitative polymerase chain reaction confirmed individual miR-144 expression levels of subjects in the two groups. Subsequent functional studies in normal and sickle erythroid progenitors showed NRF2 gene silencing by miR-144 and concomitant repression of γ-globin transcription; by contrast, treatment with miR-144 antagomir reversed its silencing effects in a dose-dependent manner. Because NRF2 regulates reactive oxygen species levels, additional studies investigated mechanisms of HbF regulation using a hemin-induced oxidative stress model. Treatment of KU812 cells with hemin produced an increase in NRF2 expression and HbF induction that reversed with miR-144 pretreatment. Chromatin immunoprecipitation assay confirmed NRF2 binding to the γ-globin antioxidant response element, which was inhibited by miR-144 mimic treatment. The genome-wide miRNA microarray and primary erythroid progenitor data support a miR-144/NRF2-mediated mechanism of γ-globin gene regulation in SCD.

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Section: Resultsmentioning

confidence: 98%

MIR-144-mediated NRF2 gene silencing inhibits fetal hemoglobin expression in sickle cell disease

Zhu

Ward

et al. 2019

Experimental Hematology

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“…The normalization of the levels with miR-16 might have been less sensitive to detect variations of less abundant miRNAs. The previous report showed that miR-451, miR-15b and 16 increased with hemolysis [ 19 , 20 , 21 ] suggesting that circulating miR-16 is not suitable internal control in hemolytic condition. We propose that target miRNA-oriented adjustment of the concentration of spiked-in cel-miR-39 is relevant to achieve stable results.…”

Section: Discussionmentioning

confidence: 99%

“…Blood cells are the main origins of circulating miRNAs [ 5 , 15 , 16 ]. Red blood cells contain an erythroid-specific miRNA (miR-451), which is released from old or pathological red blood cells in hemolytic diseases [ 11 , 17 - 20 ].…”

Section: Introductionmentioning

confidence: 99%

The Influence of Pre-analytical Factors on the Analysis of Circulating MicroRNA

Shiotsu

Okada

Shibuta

et al. 2018

MIRNA

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Background: MicroRNAs (miRNA) are expected as useful biomarkers for various diseases. We studied the pre-analytical factors causing variation in the analysis of miRNA.Material and Methods: Blood samples were collected from 25 healthy subjects. Plasma and serum were obtained from the same samples. The levels of miR-451, -16, -126, and -223 were analyzed using RT-qPCR. Cel-miR-39 was added as a spiked-in control in each sample.Results: With the exception of miR-451, the levels of the miRNAs in plasma were higher than in serum. After high-speed centrifugation, the levels of miRNAs were almost equal between plasma and serum except for miR-451. Membrane filtration with 0.45 µm pore size reduced the levels of plasma miRNAs. The coagulation accelerators for serum processing did not affect the analysis of miRNA. The use of fraction containing particles of > 0.45 µm in size showed the inhibitory effect on the analysis of plasma miR-451. The RNase inhibitor was effective for protecting against the degradation of miRNAs.Conclusion: Plasma contains factors modifying miRNA profiles. The immediate processing of plasma with membrane filtration and RNase inhibitor may be a relevant method for achieving the stable analysis of miRNA

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“…Liu et al (15) reported that miRNA-451 protected neurons against IRI-induced cell death. Leecharoenkiat et al (16) showed that miRNA-451 levels may be associated with β-thalassemia/hemoglobin-E. The present study aimed to investigate the role of miRNA-451 on cerebral ischemia-reperfusion and its possible mechanism.…”

Section: Introductionmentioning

confidence: 88%

MicroRNA‑451 relieves inflammation in cerebral ischemia‑reperfusion via the Toll‑like receptor 4/MyD88/NF‑κB signaling pathway

Dong

Chu

et al. 2019

Mol Med Report

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The present study was designed to investigate the role of microRNA-451 (miRNA-451) on cerebral ischemia-reperfusion and to explore its possible mechanism. The expression of miRNA-451 was downregulated in rats with cerebral ischemia-reperfusion. In an in vitro model of cerebral ischemia-reperfusion, the downregulation of miRNA-451 increased inflammation, demonstrated by increased levels of tumor necrosis factor α, interleukin (IL)-1b, IL-6 and IL-18. However, the upregulation of miRNA-451 expression decreased inflammation in the same in vitro model of cerebral ischemia-reperfusion. In addition, it was found that the downregulation of miRNA-451 induced the expression of Toll-like receptor 4 (TLR4), myeloid differentiation primary response protein MyD88 (MyD88) and nuclear factor-κB (NF-κB)/p65. Moreover, the administration of a MyD88 inhibitor, ST 2825, reduced the expression of MyD88 and NF-κB/p65 in the in vitro model of cerebral ischemia-reperfusion, inhibiting the effects of miRNA-451 upregulation on inflammation. A TLR4 inhibitor, TAK-242, was used to reduce the expression of TLR4 in the in vitro model of cerebral ischemia-reperfusion. TAK-242 suppressed the effects of miRNA-451 downregulation on inflammation. The present study suggested that miRNA-451 regulated cerebral ischemia-reperfusion-induced inflammation, which is mediated through the TLR4/MyD88/NF-κB signaling pathway.

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Plasma microRNA-451 as a novel hemolytic marker for β0-thalassemia/HbE disease

Cited by 23 publications

References 34 publications

MIR-144-mediated NRF2 gene silencing inhibits fetal hemoglobin expression in sickle cell disease

MIR-144-mediated NRF2 gene silencing inhibits fetal hemoglobin expression in sickle cell disease

The Influence of Pre-analytical Factors on the Analysis of Circulating MicroRNA

MicroRNA‑451 relieves inflammation in cerebral ischemia‑reperfusion via the Toll‑like receptor 4/MyD88/NF‑κB signaling pathway

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