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Related Concept Videos

MicroRNAs01:22

MicroRNAs

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MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
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MicroRNAs01:22

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MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After...
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MicroRNA Amplification and Recognition through Locked-nucleic-acid In situ Hybridization as A Novel Detection and Quantification Method
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Identification of miRNAs that regulate human CYP2B6 expression.

Masataka Nakano1, Chika Iwakami2, Tatsuki Fukami1

  • 1Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi, Kanazawa, 920-1192, Japan; WPI Nano Life Science Institute (WPI-NanoLSI) Kanazawa University, Kakuma-machi, Kanazawa, 920-1192, Japan.

Drug Metabolism and Pharmacokinetics
|April 19, 2021
PubMed
Summary

MicroRNAs (miRNAs) regulate human hepatic cytochrome P450 2B6 (CYP2B6) expression. Specifically, miR-145, miR-194, miR-222, and miR-378 negatively control CYP2B6 levels by binding to its 3'-untranslated region.

Keywords:
3′-untranslated regionCYP2B6Drug metabolizing enzymePosttranscriptional regulationmicroRNA

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Identifying Targets of Human microRNAs with the LightSwitch Luciferase Assay System using 3'UTR-reporter Constructs and a microRNA Mimic in Adherent Cells
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Identifying Targets of Human microRNAs with the LightSwitch Luciferase Assay System using 3'UTR-reporter Constructs and a microRNA Mimic in Adherent Cells
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Genome-wide Screen for miRNA Targets Using the MISSION Target ID Library
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Genome-wide Screen for miRNA Targets Using the MISSION Target ID Library

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Area of Science:

  • Pharmacogenomics
  • Molecular Biology
  • Drug Metabolism

Background:

  • Human hepatic cytochrome P450 2B6 (CYP2B6) is crucial for metabolizing numerous drugs.
  • Moderate correlation between CYP2B6 mRNA and protein levels suggests posttranscriptional regulation.

Purpose of the Study:

  • To investigate the role of microRNAs (miRNAs) in the posttranscriptional regulation of CYP2B6.
  • To identify specific miRNAs that target and regulate CYP2B6 expression.

Main Methods:

  • Established HEK293 cell lines stably expressing CYP2B6 with or without the 3 acronym{'-'}untranslated region (3 acronym{'-'}UTR).
  • Tested 14 predicted miRNAs for their effect on CYP2B6 protein levels and activity.
  • Analyzed the correlation between miRNA expression and CYP2B6 translational efficiency.

Main Results:

  • Overexpression of miR-145, miR-194, miR-222, and miR-378 significantly decreased CYP2B6 protein levels and activity in cells with the 3 acronym{'-'}UTR.
  • These miRNAs negatively regulate CYP2B6 by binding to its 3 acronym{'-'}UTR.
  • No direct negative correlation was found between individual miRNA expression and CYP2B6 translational efficiency, suggesting a complex regulatory network.

Conclusions:

  • Human CYP2B6 expression is posttranscriptionally regulated by miR-145, miR-194, miR-222, and miR-378.
  • These miRNAs exert their regulatory function through interaction with the 3 acronym{'-'}UTR of CYP2B6 mRNA.
  • Multiple miRNAs likely contribute to the overall regulation of CYP2B6 expression.