Evidence map›Paper›PMID 24399855›Full record

ArticleThe Journal of pharmacology and experimental therapeutics2014

Regulation of UDP-glucuronosyltransferase 1A1 expression and activity by microRNA 491-3p.

Douglas F Dluzen, Dongxiao Sun, Anna C Salzberg, Nate Jones, Ryan T Bushey, Gavin P Robertson, Philip Lazarus

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of pharmacology and experimental therapeutics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
4.1field-weighted citation impact, top 5% 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

34 citing papers in PubMed, 75 citations in OpenAlex.

  1. Article
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  6. Novel Approaches to Characterize Individual Drug Metabolism and Advance Precision Medicine.Drug metabolism and disposition: the biological fate of chemicals · 2023
    Review
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  9. Article
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  16. Article
  17. Regulation of UGT2A1 by miR-196a-5p and miR-196b-5p.The Journal of pharmacology and experimental therapeutics · 2019
    Article
  18. Review
  19. Article
  20. 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

7 authors at 2 institutions in 1 country.

Douglas F DluzenDepartments of Pharmacology (D.F.D., D.S., N.J., R.T.B., G.P.R., P.L.) and Public Health Sciences (A.C.S.), Penn State University College of Medicine, Hershey, Pennsylvania; and Department of Pharmaceutical Sciences, Washington State University College of Pharmacy, Spokane, Washington (P.L.).
Dongxiao Sun
Anna C Salzberg
Nate Jones
Ryan T Bushey
Gavin P Robertson
Philip Lazarus
Pennsylvania State University · USWashington State University Spokane · US

Funding

Penn State Clinical and Translational Science InstituteUL1TR000127 · NCATS · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · PI SINOWAY, LAWRENCE I · 2012 to 2015
$17.1M
UDPGLUCURONOSYLTRANSFERASE GENOTYPE AND ORAL CANCER RISKR01DE013158 · NIDCR · UNIVERSITY OF SOUTH FLORIDA · PI LAZARUS, PHILIP · 2000 to 2011
$3.6M
NCATS NIH HHS UL1 TR000127NCATS NIH HHS UL1-TR000127NIDCR NIH HHS R01 DE013158NIDCR NIH HHS R01-DE13158
6 · The paper itself

Abstract

The UDP-glucuronosyltransferase (UGT) 1A enzymes are involved in the phase II metabolism of many important endogenous and exogenous compounds. The nine UGT1A isoforms exhibit high interindividual differences in expression, but their epigenetic regulation is not well understood. The purpose of the present study was to examine microRNA (miRNA) regulation of hepatic UGT1A enzymes and determine whether or not that regulation impacts enzymatic activity. In silico analysis identified miRNA 491-3p (miR-491-3p) as a potential regulator of the UGT1A gene family via binding to the shared UGT1A 3'-untranslated region common to all UGT1A enzymes. Transfection of miR-491-3p mimic into HuH-7 cells significantly repressed UGT1A1 (P < 0.001), UGT1A3 (P < 0.05), and UGT1A6 (P < 0.05) mRNA levels. For UGT1A1, this repression correlated with significantly reduced metabolism of raloxifene into raloxifene-6-glucuronide (ral-6-gluc; P < 0.01) and raloxifene-4'-glucuronide (ral-4'-gluc; P < 0.01). In HuH-7 cells with repressed miR-491-3p expression, there was a significant increase (~80%; P < 0.01) in UGT1A1 mRNA and a corresponding increase in glucuronidation of raloxifene into ral-6-gluc (50%; P < 0.05) and ral-4'-gluc (22%; P < 0.01). Knockdown of endogenous miR-491-3p in HepG2 cells did not significantly alter UGT1A1 mRNA levels but did increase the formation of ral-6-gluc (50%; P < 0.05) and ral-4'-gluc (34%; P < 0.001). A significant inverse correlation between miR-491-3p expression and both UGT1A3 (P < 0.05) and UGT1A6 (P < 0.01) mRNA levels was observed in a panel of normal human liver specimens, with a significant (P < 0.05) increase in UGT1A3 and UGT1A6 mRNA levels observed in miR-491-3p nonexpressing versus expressing liver specimens. These results suggest that miR-491-3p is an important factor in regulating the expression of UGT1A enzymes in vivo.

Indexed as

Cell Line, TumorComputer SimulationEpirubicinGlucuronidesGlucuronosyltransferaseHEK293 CellsHumansLiverLuciferases, RenillaMicroRNAsOrgan SpecificityProtein BindingRaloxifene HydrochlorideRNA, MessengerUGT1A1 EnzymeEpirubicinGlucuronidesGlucuronosyltransferaseLuciferases, RenillaMicroRNAsMIRN491 microRNA, humanRaloxifene HydrochlorideRNA, MessengerUGT1A1 Enzyme

Identifiers

PMID24399855
PMCPMC3935146
OpenAlexW2137285308

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.