Genome-wide microRNA profiles identify miR-107 as a top miRNA associating with expression of the CYP3As and other drug metabolizing cytochrome P450 enzymes in the liver

Tantawy, M.; Collins, Joseph M.; Wang, Daqing

doi:10.3389/fphar.2022.943538

Cited by 10 publications

(4 citation statements)

References 67 publications

(101 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The further construction of the lncRNA/circRNA-miRNA-mRNA-pathway regulation network showed that miR-1260 and miR-107_R-2 were involved in the regulation of the glycerolipid metabolism pathway. It was found that miR-1260 and miR-107 were closely related to the expression of cytochrome P450 (CYP) enzymes, including CYP3A4, CYP3A5, and CYP3A43 [51]. MiR-107 is highly expressed in the skeletal muscle of Qinchuan cattle, and circFGFR4 can promote myoblast differentiation by binding with miR-107 [52].…”

Section: Discussionmentioning

confidence: 99%

Whole-Transcriptome RNA Sequencing Uncovers the Global Expression Changes and RNA Regulatory Networks in Duck Embryonic Myogenesis

Liu,

Wu,

Zhang

et al. 2023

IJMS

View full text Add to dashboard Cite

Duck meat is pivotal in providing high-quality protein for human nutrition, underscoring the importance of studying duck myogenesis. The regulatory mechanisms governing duck myogenesis involve both coding and non-coding RNAs, yet their specific expression patterns and molecular mechanisms remain elusive. To address this knowledge gap, we performed expression profiling analyses of mRNAs, lncRNAs, circRNAs, and miRNAs involved in duck myogenesis using whole-transcriptome RNA-seq. Our analysis identified 1733 differentially expressed (DE)-mRNAs, 1116 DE-lncRNAs, 54 DE-circRNAs, and 174 DE-miRNAs when comparing myoblasts and myotubes. A GO analysis highlighted the enrichment of DE molecules in the extracellular region, protein binding, and exocyst. A KEGG analysis pinpointed pathways related to ferroptosis, PPAR signaling, nitrogen metabolism, cell cycle, cardiac muscle contraction, glycerolipid metabolism, and actin cytoskeleton. A total of 51 trans-acting lncRNAs, including ENSAPLT00020002101 and ENSAPLT00020012069, were predicted to participate in regulating myoblast proliferation and differentiation. Based on the ceRNAs, we constructed lncRNA-miRNA-mRNA and circRNA-miRNA-mRNA ceRNA networks involving five miRNAs (miR-129-5p, miR-133a-5p, miR-22-3p, miR-27b-3p, and let-7b-5p) that are relevant to myogenesis. Furthermore, the GO and KEGG analyses of the DE-mRNAs within the ceRNA network underscored the significant enrichment of the glycerolipid metabolism pathway. We identified five different DE-mRNAs, specifically ENSAPLG00020001677, ENSAPLG00020002183, ENSAPLG00020005019, ENSAPLG00020010497, and ENSAPLG00020017682, as potential target genes that are crucial for myogenesis in the context of glycerolipid metabolism. These five mRNAs are integral to ceRNA networks, with miR-107_R-2 and miR-1260 emerging as key regulators. In summary, this study provides a valuable resource elucidating the intricate interplay of mRNA-lncRNA-circRNA-miRNA in duck myogenesis, shedding light on the molecular mechanisms that govern this critical biological process.

show abstract

Section: Discussionmentioning

confidence: 99%

Whole-Transcriptome RNA Sequencing Uncovers the Global Expression Changes and RNA Regulatory Networks in Duck Embryonic Myogenesis

Liu,

Wu,

Zhang

et al. 2023

IJMS

View full text Add to dashboard Cite

show abstract

“…The interrelated roles of miRNA, lncRNA, and genetic polymorphisms in regulating PXR expression are reviewed extensively by Smutny et al (2021 ). A recent ex vivo study by Tantawy et al found significant associations between miR-107 and nine different transcription factors that regulate expression of CYP3A enzymes; the transcription factors include estrogen receptor alpha ( ESR1 ), PXR, hepatocyte nuclear factor 3-beta ( FOXA2 ), HNF4A , and peroxisome proliferator activated receptor alpha ( PPARA ) ( Tantawy et al, 2022 ). These results suggest that miR-107 does not directly regulate CYP3A expression by binding to mRNA for CYP3As; rather, miR-107 may modulate the expression of multiple key transcription factors affecting P450 expression ( Tantawy et al, 2022 ).…”

Section: Circulating Ncrnasmentioning

confidence: 99%

“…A recent ex vivo study by Tantawy et al found significant associations between miR-107 and nine different transcription factors that regulate expression of CYP3A enzymes; the transcription factors include estrogen receptor alpha ( ESR1 ), PXR, hepatocyte nuclear factor 3-beta ( FOXA2 ), HNF4A , and peroxisome proliferator activated receptor alpha ( PPARA ) ( Tantawy et al, 2022 ). These results suggest that miR-107 does not directly regulate CYP3A expression by binding to mRNA for CYP3As; rather, miR-107 may modulate the expression of multiple key transcription factors affecting P450 expression ( Tantawy et al, 2022 ). As liquid biopsy analysis of cfRNA in exosomes continues to gain interest, it is important to note that a mechanism for the association between circulating exosomal miRNA and the metabolic clearance rates of DME substrates remains largely unknown ( Pridgeon et al, 2022 ).…”

Section: Circulating Ncrnasmentioning

confidence: 99%

Novel Approaches to Characterize Individual Drug Metabolism and Advance Precision Medicine

et al. 2023

View full text Add to dashboard Cite

Interindividual variability in drug metabolism can significantly affect drug concentrations in the body and subsequent drug response. Understanding an individual’s drug metabolism capacity is important for predicting drug exposure and developing precision medicine strategies. The goal of precision medicine is to individualize drug treatment for patients to maximize efficacy and minimize drug toxicity. While advances in pharmacogenomics have improved our understanding of how genetic variations in drug-metabolizing enzymes (DMEs) affect drug response, nongenetic factors are also known to influence drug metabolism phenotypes. This minireview discusses approaches beyond pharmacogenetic testing to phenotype DMEs—particularly the cytochrome P450 enzymes—in clinical settings. Several phenotyping approaches have been proposed: traditional approaches include phenotyping with exogenous probe substrates and the use of endogenous biomarkers; newer approaches include evaluating circulating noncoding RNAs and liquid biopsy-derived markers relevant to DME expression and function. The goals of this minireview are to 1) provide a high-level overview of traditional and novel approaches to phenotype individual drug metabolism capacity, 2) describe how these approaches are being applied or can be applied to pharmacokinetic studies, and 3) discuss perspectives on future opportunities to advance precision medicine in diverse populations. SIGNIFICANCE STATEMENT This minireview provides an overview of recent advances in approaches to characterize individual drug metabolism phenotypes in clinical settings. It highlights the integration of existing pharmacokinetic biomarkers with novel approaches; also discussed are current challenges and existing knowledge gaps. The article concludes with perspectives on the future deployment of a liquid biopsy-informed physiologically based pharmacokinetic strategy for patient characterization and precision dosing.

show abstract

“…Differences in drug metabolism between males and females often lead to distinct AEs due to higher expression and activity of CYP3A enzyme for females than males [14]. Midazolam is a widely used hypnotic metabolized by CYP3A in the liver, and pharmacokinetic differences between males and females have been reported [15].…”

Section: Real Data Analysismentioning

confidence: 99%

Model Driven Method for exploring Individual and Confounding Effects in Spontaneous Adverse Event Reporting Databases

Liu

Shi

Pan

2023

Preprint

View full text Add to dashboard Cite

Background Spontaneous Adverse Event Reporting (SAER) databases play a crucial part in post-marketed drug surveillance. The reported odds ratio (ROR) is commonly used to detect the significant signal of AE-drug combinations. However, the typical ROR may be biased by heterogeneity from individual factors such as gender and age. In addition, confounding biases render the typical ROR far from indicative of causality. Therefore, these issues urgently require solutions. Methods Model driven ROR (MD-ROR) was proposed as an alternative to typical ROR to explore individual and confounding effects in SAER databases. Unlike the traditional 2*2 cross table approach, our method employed Poisson regression with two-way interactions to estimate the MD-ROR, which was shown to be equivalent to typical ROR. Subsequently, we introduce the MD-ROR under three-way interaction to reveal the heterogeneity behind pooled crude ROR and to identify subgroup effects on the signals of AE-drugs. We also introduce adjusted MD-ROR to address confounding biases by flexibly defining confound effects in the model. To test our methods, the simulation data and FDA Adverse Event Reporting System (FAERS) database were both used. Result The simulated data suggested the subgroup effects estimated by MD-ROR were unbiased and efficient. Additionally, the adjusted MD-ROR was more robust against confounding biases than crude ROR. Application of our method to FAERS database showed differences in drug interaction and cardiac adverse events between males and females for Midazolam existed. In addition, the AE-drug combinations, Midazolam-septic shock and Midazolam-depression, were found overestimated potentially due to confounding biases from gender. Conclusion Our study highlighted that MD-ROR is a promising method for exploring individual and confounding effects in SAER databases. Our method provides a bridge between SAER databases and flexibly customized models.

show abstract

Genome-wide microRNA profiles identify miR-107 as a top miRNA associating with expression of the CYP3As and other drug metabolizing cytochrome P450 enzymes in the liver

Cited by 10 publications

References 67 publications

Whole-Transcriptome RNA Sequencing Uncovers the Global Expression Changes and RNA Regulatory Networks in Duck Embryonic Myogenesis

Whole-Transcriptome RNA Sequencing Uncovers the Global Expression Changes and RNA Regulatory Networks in Duck Embryonic Myogenesis

Novel Approaches to Characterize Individual Drug Metabolism and Advance Precision Medicine

Model Driven Method for exploring Individual and Confounding Effects in Spontaneous Adverse Event Reporting Databases

Contact Info

Product

Resources

About