Abstract
Background: The important role of nuclear receptors in transcriptional gene regulation of drug-metabolizing enzymes (DMEs) and drug transporters (DTs) has been well documented. In contrast, there is limited understanding of post-transcriptional gene regulation of DMEs and DTs. MicroRNAs (miRNAs) represent a large group of non-coding RNAs that control the post-transcriptional expression of target genes. Currently, > 800 miRNAs have been identified in human genome, which are believed to regulate thousands of human protein-coding genes. Objective: This review aims to discuss the potential role of miRNAs in drug metabolism and disposition, following an introduction of miRNA biogenesis, regulatory mechanisms, and target identification and validation. Results/conclusions: Some miRNAs have been shown to directly or indirectly control the expression of DMEs, DTs or nuclear receptors, and consequently, affect the capacity of drug metabolism and disposition, and influence the sensitivity of cells to xenobiotic agents. Furthermore, the expression of some miRNAs is readily altered in cells after an acute or chronic exposure to medications, toxins or carcinogens. Therefore, dysregulation of specific miRNAs by a xenobiotic agent, which control the expression of DMEs or DTs, might lead to considerable change in the pharmacokinetic and pharmacodynamic property of a concomitant drug or the agent itself. Improved understanding of the regulatory pathways of DMEs and DTs shall provide novel insight into multi-drug resistance and potential drugdrug interaction in clinical pharmacotherapy as well as in drug discovery and development.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1513-1528 |
| Number of pages | 16 |
| Journal | Expert Opinion on Drug Metabolism and Toxicology |
| Volume | 5 |
| Issue number | 12 |
| DOIs | |
| State | Published - Dec 2009 |
| Externally published | Yes |
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Keywords
- Cancer
- Drug interaction
- Drug metabolism
- Gene regulation
- MicroRNA
- Multi-drug resistance
- Nuclear receptor
- Transporter
ASJC Scopus subject areas
- Toxicology
- Pharmacology
Cite this
Role of microRNAs in the regulation of drug metabolism and disposition. / Yu, Aiming.
In: Expert Opinion on Drug Metabolism and Toxicology, Vol. 5, No. 12, 12.2009, p. 1513-1528.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Role of microRNAs in the regulation of drug metabolism and disposition
AU - Yu, Aiming
PY - 2009/12
Y1 - 2009/12
N2 - Background: The important role of nuclear receptors in transcriptional gene regulation of drug-metabolizing enzymes (DMEs) and drug transporters (DTs) has been well documented. In contrast, there is limited understanding of post-transcriptional gene regulation of DMEs and DTs. MicroRNAs (miRNAs) represent a large group of non-coding RNAs that control the post-transcriptional expression of target genes. Currently, > 800 miRNAs have been identified in human genome, which are believed to regulate thousands of human protein-coding genes. Objective: This review aims to discuss the potential role of miRNAs in drug metabolism and disposition, following an introduction of miRNA biogenesis, regulatory mechanisms, and target identification and validation. Results/conclusions: Some miRNAs have been shown to directly or indirectly control the expression of DMEs, DTs or nuclear receptors, and consequently, affect the capacity of drug metabolism and disposition, and influence the sensitivity of cells to xenobiotic agents. Furthermore, the expression of some miRNAs is readily altered in cells after an acute or chronic exposure to medications, toxins or carcinogens. Therefore, dysregulation of specific miRNAs by a xenobiotic agent, which control the expression of DMEs or DTs, might lead to considerable change in the pharmacokinetic and pharmacodynamic property of a concomitant drug or the agent itself. Improved understanding of the regulatory pathways of DMEs and DTs shall provide novel insight into multi-drug resistance and potential drugdrug interaction in clinical pharmacotherapy as well as in drug discovery and development.
AB - Background: The important role of nuclear receptors in transcriptional gene regulation of drug-metabolizing enzymes (DMEs) and drug transporters (DTs) has been well documented. In contrast, there is limited understanding of post-transcriptional gene regulation of DMEs and DTs. MicroRNAs (miRNAs) represent a large group of non-coding RNAs that control the post-transcriptional expression of target genes. Currently, > 800 miRNAs have been identified in human genome, which are believed to regulate thousands of human protein-coding genes. Objective: This review aims to discuss the potential role of miRNAs in drug metabolism and disposition, following an introduction of miRNA biogenesis, regulatory mechanisms, and target identification and validation. Results/conclusions: Some miRNAs have been shown to directly or indirectly control the expression of DMEs, DTs or nuclear receptors, and consequently, affect the capacity of drug metabolism and disposition, and influence the sensitivity of cells to xenobiotic agents. Furthermore, the expression of some miRNAs is readily altered in cells after an acute or chronic exposure to medications, toxins or carcinogens. Therefore, dysregulation of specific miRNAs by a xenobiotic agent, which control the expression of DMEs or DTs, might lead to considerable change in the pharmacokinetic and pharmacodynamic property of a concomitant drug or the agent itself. Improved understanding of the regulatory pathways of DMEs and DTs shall provide novel insight into multi-drug resistance and potential drugdrug interaction in clinical pharmacotherapy as well as in drug discovery and development.
KW - Cancer
KW - Drug interaction
KW - Drug metabolism
KW - Gene regulation
KW - MicroRNA
KW - Multi-drug resistance
KW - Nuclear receptor
KW - Transporter
UR - http://www.scopus.com/inward/record.url?scp=71049182620&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=71049182620&partnerID=8YFLogxK
U2 - 10.1517/17425250903307448
DO - 10.1517/17425250903307448
M3 - Article
C2 - 19785514
AN - SCOPUS:71049182620
VL - 5
SP - 1513
EP - 1528
JO - Expert Opinion on Drug Metabolism and Toxicology
JF - Expert Opinion on Drug Metabolism and Toxicology
SN - 1742-5255
IS - 12
ER -