Evidence map›Paper›PMID 27474751›Full record

ArticleThe Journal of pharmacology and experimental therapeutics2016

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

Douglas F Dluzen, Aimee K Sutliff, Gang Chen, Christy J W Watson, Faoud T Ishmael, Philip Lazarus

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of pharmacology and experimental therapeutics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
2.9field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

17 citing papers in PubMed, 52 citations in OpenAlex.

  1. Review
  2. Novel Approaches to Characterize Individual Drug Metabolism and Advance Precision Medicine.Drug metabolism and disposition: the biological fate of chemicals · 2023
    Review
  3. Article
  4. Review
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  13. Regulation of UGT2A1 by miR-196a-5p and miR-196b-5p.The Journal of pharmacology and experimental therapeutics · 2019
    Article
  14. Review
  15. Article
  16. Article
  17. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 4 institutions in 1 country.

Douglas F DluzenNational 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.).
Aimee K SutliffNational 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.).
Gang ChenNational 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.).
Christy J W WatsonNational 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.).
Faoud T IshmaelNational 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.).
Philip LazarusNational 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.) phil.lazarus@wsu.edu.
National Institute on Aging · USNational Institutes of Health · USPennsylvania State University · USWashington State University Spokane · US

Funding

UDPGLUCURONOSYLTRANSFERASE GENOTYPE AND ORAL CANCER RISKR01DE013158 · NIDCR · UNIVERSITY OF SOUTH FLORIDA · PI LAZARUS, PHILIP · 2000 to 2011
$3.6M
The UGT2A and 3A metabolizing enzymes and tobacco-related cancer riskR01ES025460 · NIEHS · WASHINGTON STATE UNIVERSITY · PI LAZARUS, PHILIP · 2015 to 2019
$2.8M
NIDCR NIH HHS R01 DE013158NIEHS NIH HHS R01 ES025460
6 · The paper itself

Abstract

The UDP-glucuronosyltransferase (UGT) 2B enzymes are important in the detoxification of a variety of endogenous and exogenous compounds, including many hormones, drugs, and carcinogens. Identifying novel mechanisms governing their expression is important in understanding patient-specific response to drugs and cancer risk factors. In silico prediction algorithm programs were used to screen for microRNAs (miRNAs) as potential regulators of UGT2B enzymes, with miR-216b-5p identified as a potential candidate. Luciferase data suggested the presence of a functional miR-216b-5p binding motif within the 3' untranslated regions of UGTs 2B7, 2B4, and 2B10. Overexpression of miR-216b-5p mimics significantly repressed UGT2B7 (P < 0.001) and UGT2B10 (P = 0.0018) mRNA levels in HuH-7 cells and UGT2B4 (P < 0.001) and UGT2B10 (P = 0.018) mRNA in Hep3B cells. UGT2B7 protein levels were repressed in both HuH-7 and Hep3B cells in the presence of increasing miR-216b-5p concentrations, corresponding with significant (P < 0.001 and P = 0.011, respectively) decreases in glucuronidation activity against the UGT2B7-specific substrate epirubicin. Inhibition of endogenous miR-216b-5p levels significantly increased UGT2B7 mRNA levels in HuH-7 (P = 0.021) and Hep3B (P = 0.0068) cells, and increased epirubicin glucuronidation by 85% (P = 0.057) and 50% (P = 0.012) for HuH-7 and Hep3B cells, respectively. UGT2B4 activity against codeine and UGT2B10 activity against nicotine were significantly decreased in both HuH-7 and Hep3B cells (P < 0.001 and P = 0.0048, and P = 0.017 and P = 0.043, respectively) after overexpression of miR-216b-5p mimic. This is the first evidence that miRNAs regulate UGT 2B7, 2B4, and 2B10 expression, and that miR-216b-5p regulation of UGT2B proteins may be important in regulating the metabolism of UGT2B substrates.

Indexed as

Gene Expression Regulation, Neoplastic3' Untranslated RegionsBase SequenceCell Line, TumorGlucuronosyltransferaseHumansLiver NeoplasmsMicroRNAsPolymorphism, Genetic3' Untranslated RegionsGlucuronosyltransferaseMicroRNAsMIRN216 microRNA, human

Identifiers

PMID27474751
PMCPMC5034702
OpenAlexW2501244830

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.