Related Experiment Video

Updated: Mar 17, 2026

Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
11:44

Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis

Published on: March 30, 2019

8.1K

Regulation of UGT2B Expression and Activity by miR-216b-5p in Liver Cancer Cell Lines

Douglas F Dluzen1, Aimee K Sutliff1, Gang Chen1

  • 1National Institute on Aging, National Institutes of Health, Baltimore, Maryland (D.F.D.); Department of Pulmonary Medicine, Penn State University College of Medicine, Hershey, Pennsylvania (F.T.I.); and Department of Pharmaceutical Sciences, Washington State University College of Pharmacy, Spokane, Washington (A.K.S., G.C., C.W., P.L.).

The Journal of Pharmacology and Experimental Therapeutics
|July 31, 2016
PubMed

Insights

MicroRNAs regulate UDP-glucuronosyltransferase (UGT) 2B enzymes, crucial for drug and carcinogen detoxification. This study identifies miR-216b-5p as a key regulator impacting UGT2B7, UGT2B4, and UGT2B10 expression and activity.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Pharmacology

Background:

  • UDP-glucuronosyltransferase (UGT) 2B enzymes are critical for metabolizing endogenous and exogenous compounds, influencing drug response and cancer risk.
  • Understanding the regulation of UGT2B enzymes is vital for personalized medicine and assessing carcinogen exposure.
  • MicroRNAs (miRNAs) are emerging as key post-transcriptional regulators of gene expression.

Purpose of the Study:

  • To identify and characterize microRNAs that regulate the expression of UGT2B enzymes.
  • To investigate the functional role of miR-216b-5p in controlling UGT2B7, UGT2B4, and UGT2B10 expression and activity.
  • To establish the significance of miRNA-mediated UGT2B regulation in cellular metabolism.

Main Methods:

  • In silico screening to predict potential miRNA regulators of UGT2B enzymes.
  • Luciferase assays to confirm miRNA binding sites in UGT 3' UTRs.
  • Overexpression and inhibition studies of miR-216b-5p in HuH-7 and Hep3B cell lines.
  • Quantitative analysis of UGT2B mRNA and protein levels.
  • Measurement of UGT enzyme activity using specific substrates (epirubicin, codeine, nicotine).

Main Results:

  • miR-216b-5p was identified as a potential regulator, with functional binding sites in UGT2B7, UGT2B4, and UGT2B10.
  • Overexpression of miR-216b-5p significantly repressed UGT2B7, UGT2B4, and UGT2B10 mRNA and protein levels.
  • miR-216b-5p overexpression led to decreased glucuronidation activity for UGT2B7 (epirubicin), UGT2B4 (codeine), and UGT2B10 (nicotine).
  • Inhibition of endogenous miR-216b-5p increased UGT2B7 mRNA levels and epirubicin glucuronidation activity.

Conclusions:

  • This study provides the first evidence that miRNAs regulate UGT2B7, UGT2B4, and UGT2B10 expression.
  • miR-216b-5p acts as a negative regulator of UGT2B enzymes, impacting their metabolic functions.
  • The miR-216b-5p-UGT2B interaction is a significant mechanism influencing the metabolism of UGT2B substrates and potentially patient drug responses.

More Related Videos

In Vitro Cultivation Techniques for Modeling Liver Organogenesis, Building Assembloids, and Designing Synthetic Tissues using Human Cell Lines08:50

In Vitro Cultivation Techniques for Modeling Liver Organogenesis, Building Assembloids, and Designing Synthetic Tissues using Human Cell Lines

Published on: April 18, 2025

1.0K
Genome-wide Screen for miRNA Targets Using the MISSION Target ID Library08:40

Genome-wide Screen for miRNA Targets Using the MISSION Target ID Library

Published on: April 6, 2012

18.1K

Related Concept Videos

MicroRNAs01:22

MicroRNAs

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...
4.2K
MicroRNAs01:22

MicroRNAs

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...
24.5K
Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase01:27

Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase

Phase II biotransformation reactions are essential for detoxifying and eliminating xenobiotics, including many pharmaceutical compounds. These reactions typically involve conjugation, the covalent attachment of polar endogenous groups such as glucuronic acid, sulfate, methyl, or acetyl moieties to functional groups introduced during Phase I metabolism. The resulting conjugates are more water-soluble, enabling efficient renal or biliary excretion.The major classes of Phase II enzymes include...
57
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
5.0K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
5.4K
Cell Specific Gene Expression01:58

Cell Specific Gene Expression

Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
16.8K