Evidence map›Paper›PMID 24302561›Full record

ArticleMolecular pharmacology2014

Morphine regulates expression of μ-opioid receptor MOR-1A, an intron-retention carboxyl terminal splice variant of the μ-opioid receptor (OPRM1) gene via miR-103/miR-107.

Zhigang Lu, Jin Xu, Mingming Xu, Gavril W Pasternak, Ying-Xian Pan

Open access · bronzeAbstract read
In one paragraph

Article in Molecular pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
1.8field-weighted citation impact, top 17% 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

30 citing papers in PubMed, 42 citations in OpenAlex.

  1. Association ofRadiology and oncology · 2023
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  5. Epigenetic Modulation of Opioid Receptors by Drugs of Abuse.International journal of molecular sciences · 2022
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  7. Review
  8. Review
  9. Morphine modulates the expression of mu-opioid receptor exon 5-associated full-length C-terminal splice variants by upregulating miR-378a-3p.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020
    Article
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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

5 authors at 1 institution in 1 country.

Zhigang LuDepartment of Neurology and the Molecular Pharmacology and Chemistry Program, Memorial Sloan-Kettering Cancer Center, New York, New York.
Jin Xu
Mingming Xu
Gavril W Pasternak
Ying-Xian Pan
Memorial Sloan Kettering Cancer Center · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
Synthesis &Pharmacology of Novel Opiates and SystemsR01DA006241 · NIDA · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI PAN, YING-XIAN · 1990 to 2018
$6.4M
PHARMACOLOGY OF OPIOID RECEPTOR SUBTYPESR01DA007242 · NIDA · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI PAN, YING-XIAN · 1991 to 2022
$6.0M
Characterizing exon 11 promoter of the mu opioid receptor gene, OPRMR01DA013997 · NIDA · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI PAN, YING-XIAN · 2002 to 2012
$3.3M
Biochemical Characterization of Opioid BInding SitesR56DA002615 · NIDA · SLOAN-KETTERING INST CAN RESEARCH · PI PASTERNAK, GAVRIL W · 2012 to 2013
$1.1M
Exploring functions of mu opioid receptor carboxyl termini by gene targetingR21DA029244 · NIDA · SLOAN-KETTERING INST CAN RESEARCH · PI PAN, YING-XIAN · 2010 to 2011
$522k
NCI NIH HHS CA08748NCI NIH HHS P30 CA008748NIDA NIH HHS R01 DA006241NIDA NIH HHS R01 DA007242NIDA NIH HHS R01 DA013997NIDA NIH HHS R01-DA013997NIDA NIH HHS R01-DA06241NIDA NIH HHS R01DA07242NIDA NIH HHS R21 DA029244NIDA NIH HHS R21-DA02944NIDA NIH HHS R56 DA002615NIDA NIH HHS R56-DA02615
6 · The paper itself

Abstract

The μ-opioid receptor (MOR-1) gene OPRM1 undergoes extensive alternative splicing, generating an array of splice variants. Of these variants, MOR-1A, an intron-retention carboxyl terminal splice variant identical to MOR-1 except for the terminal intracellular tail encoded by exon 3b, is quite abundant and conserved from rodent to humans. Increasing evidence indicates that miroRNAs (miRNAs) regulate MOR-1 expression and that μ agonists such as morphine modulate miRNA expression. However, little is known about miRNA regulation of the OPRM1 splice variants. Using 3'-rapid amplification cDNA end and Northern blot analyses, we identified the complete 3'-untranslated region (3'-UTR) for both mouse and human MOR-1A and their conserved polyadenylation site, and defined the role the 3'-UTR in mRNA stability using a luciferase reporter assay. Computer models predicted a conserved miR-103/107 targeting site in the 3'-UTR of both mouse and human MOR-1A. The functional relevance of miR-103/107 in regulating expression of MOR-1A protein through the consensus miR-103/107 binding sites in the 3'-UTR was established by using mutagenesis and a miR-107 inhibitor in transfected human embryonic kidney 293 cells and Be(2)C cells that endogenously express human MOR-1A. Chronic morphine treatment significantly upregulated miR-103 and miR-107 levels, leading to downregulation of polyribosome-associated MOR-1A in both Be(2)C cells and the striatum of a morphine-tolerant mouse, providing a new perspective on understanding the roles of miRNAs and OPRM1 splice variants in modulating the complex actions of morphine in animals and humans.

Indexed as

3' Untranslated RegionsAnimalsCorpus StriatumGene Expression RegulationHEK293 CellsHumansIntronsMiceMice, Inbred C57BLMicroRNAsMorphineReceptors, Opioid, mu3' Untranslated RegionsMicroRNAsMIRN103 microRNA, humanMIRN103 microRNA, mouseMIRN107 microRNA, humanMIRN107 microRNA, mouseMorphineOPRM1 protein, humanOprm protein, mouseReceptors, Opioid, mu

Identifiers

PMID24302561
PMCPMC3913361
OpenAlexW2030658643

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.