Conserved Seed Pairing, Often Flanked by Adenosines, Indicates that Thousands of Human Genes are MicroRNA Targets

Lewis, Benjamin P.; Burge, Christopher B.; Bartel, David P.

doi:10.1016/j.cell.2004.12.035

Cited by 10,785 publications

(9,629 citation statements)

References 24 publications

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“…Among the miRNA–mRNA coexpression pairs, TargetScan v7.0 (Lewis et al ., 2005; Agarwal et al ., 2015) predicted 3552 of the 4682 mRNAs to be potential corresponding targets for the coexpressed age‐associated miRNAs, including 406 of the 551 age‐associated mRNAs (~74%). Details of miRNAs and their coexpressed/predicted target mRNAs involved in each GO category are provided in Table S6.…”

Section: Resultsmentioning

confidence: 99%

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Age‐associated microRNA expression in human peripheral blood is associated with all‐cause mortality and age‐related traits

et al. 2017

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SummaryRecent studies provide evidence of correlations of DNA methylation and expression of protein‐coding genes with human aging. The relations of microRNA expression with age and age‐related clinical outcomes have not been characterized thoroughly. We explored associations of age with whole‐blood microRNA expression in 5221 adults and identified 127 microRNAs that were differentially expressed by age at P < 3.3 × 10−4 (Bonferroni‐corrected). Most microRNAs were underexpressed in older individuals. Integrative analysis of microRNA and mRNA expression revealed changes in age‐associated mRNA expression possibly driven by age‐associated microRNAs in pathways that involve RNA processing, translation, and immune function. We fitted a linear model to predict ‘microRNA age’ that incorporated expression levels of 80 microRNAs. MicroRNA age correlated modestly with predicted age from DNA methylation (r = 0.3) and mRNA expression (r = 0.2), suggesting that microRNA age may complement mRNA and epigenetic age prediction models. We used the difference between microRNA age and chronological age as a biomarker of accelerated aging (Δage) and found that Δage was associated with all‐cause mortality (hazards ratio 1.1 per year difference, P = 4.2 × 10−5 adjusted for sex and chronological age). Additionally, Δage was associated with coronary heart disease, hypertension, blood pressure, and glucose levels. In conclusion, we constructed a microRNA age prediction model based on whole‐blood microRNA expression profiling. Age‐associated microRNAs and their targets have potential utility to detect accelerated aging and to predict risks for age‐related diseases.

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Section: Resultsmentioning

confidence: 99%

“…For the coexpressed miRNA–mRNA pairs, we used TargetScan v7.0 (Lewis et al ., 2005; Agarwal et al ., 2015) to predict whether the mRNAs were the corresponding targets for the miRNAs. TargetScan predicts mRNA targets of miRNAs by searching for the presence of 8‐mer, 7‐mer, and 6‐mer sites that match the seed region of each miRNA.…”

Section: Methodsmentioning

confidence: 99%

Age‐associated microRNA expression in human peripheral blood is associated with all‐cause mortality and age‐related traits

et al. 2017

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“…It is now established that mRNA transcripts expression are the results of a transcriptional and posttranscriptional regulation by miRNAs 22, 23. Therefore, multiple evidences show that megakaryocytes transfer mRNA and miRNA to circulating platelets and that this transferred genetic code changes in different diseases 24…”

Section: Resultsmentioning

confidence: 99%

MiR‐21 role in aspirin‐dependent PPARα and multidrug resistance protein 4 upregulation

Massimi

Alemanno

Guarino

et al. 2018

Research and Practice in Thrombosis and Haemostasis

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BackgroundA mechanism involved in high on‐aspirin treatment residual platelet reactivity is platelet multidrug resistance protein 4 (MRP4) overexpression. Aspirin enhances platelet MRP4 expression with a PPARα‐dependent mechanism and reduces miR‐21 expression that, in turn, downregulates PPARα expression.ObjectiveThe aim of our study was to verify the relationship between miR‐21 and MRP4‐PPARα levels induced by aspirin treatment.MethodsWe evaluated the changes in MRP4‐PPARα, mRNA, MRP4 protein, and miR‐21 expression induced by aspirin in: (i) in vitro–treated megakaryoblastic cell line (DAMI), (ii) primary megakaryocytes cultures and derived platelets, (iii) healthy volunteers’ platelets treated with aspirin, and (iv) aspirinated patients (aspirin‐treated patients) and in a control population (control).ResultsWe observed an aspirin‐induced reverse relationship between the expression of miR‐21 and PPARα‐MRP4. In DAMI cells the miR‐21 mimic transfection reduces PPARα and MRP4 expression, even if cells were treated with aspirin after transfection. MiR‐21 inhibitor transfection induces PPARα and MRP4 expression that are not enhanced by aspirin treatment. In human megakaryocytes, aspirin treatment lead to a miR‐21 downregulation and a MRP4 upregulation and this trend is confirmed in derived platelets. In aspirin‐treated volunteers, an inverse relationship between miR‐21 and MRP4 platelet expression was found after aspirin treatment. A similar negative relationship was found in aspirin‐treated patients vs the control population.ConclusionThe results reported in this study provide information that aspirin induces the modulation of platelet miR‐21 expression levels and this modulation can be responsible for MRP4 enhancement in circulating platelets.

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“…miRNAs are also involved in several biological processes and are major regulators of cell differentiation, growth, proliferation and apoptosis 11, 12, 13. Recently, the roles of miR‐21 in cardiovascular biology and disease have received significant attention.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA‐21 protects against cardiac hypoxia/reoxygenation injury by inhibiting excessive autophagy in H9c2 cells via the Akt/mTOR pathway

Huang

Kong

et al. 2016

J Cellular Molecular Medi

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MicroRNAs and autophagy play critical roles in cardiac hypoxia/reoxygenation (H/R)‐induced injury. Here, we investigated the function of miR‐21 in regulating autophagy and identified the potential molecular mechanisms involved. To determine the role of miR‐21 in regulating autophagy, H9c2 cells were divided into the following six groups: control group, H/R group, (miR‐21+ H/R) group, (miR‐21‐negative control + H/R) group, (BEZ235+ H/R) group and (miR‐21+ BEZ235+ H/R) group. The cells underwent hypoxia for 1 hr and reoxygenation for 3 hrs. Cell count kit‐8 was used to evaluate cell function and apoptosis was analysed by Western blotting. Western blotting and transmission electron microscopy were used to investigate autophagy. We found that miR‐21 expression was down‐regulated, and autophagy was remarkably increased in H9c2 cells during H/R injury. Overexpression of miR‐21 with a miR‐21 precursor significantly inhibited autophagic activity and decreased apoptosis, accompanied by the activation of the AKT/mTOR pathway. In addition, treatment with BEZ235, a novel dual Akt/mTOR inhibitor, resulted in a significant increase in autophagy and apoptosis. However, we found that miR‐21‐mediated inhibition of apoptosis and autophagy was partly independent of Akt/mTOR activation, as demonstrated in cells treated with both miR‐21 and BEZ235. We showed that miR‐21 could inhibit H/R‐induced autophagy and apoptosis, which may be at least partially mediated by the Akt/mTOR signalling pathway.

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Conserved Seed Pairing, Often Flanked by Adenosines, Indicates that Thousands of Human Genes are MicroRNA Targets

Cited by 10,785 publications

References 24 publications

Age‐associated microRNA expression in human peripheral blood is associated with all‐cause mortality and age‐related traits

Age‐associated microRNA expression in human peripheral blood is associated with all‐cause mortality and age‐related traits

MiR‐21 role in aspirin‐dependent PPARα and multidrug resistance protein 4 upregulation

MicroRNA‐21 protects against cardiac hypoxia/reoxygenation injury by inhibiting excessive autophagy in H9c2 cells via the Akt/mTOR pathway

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