PUBLICATION

μ Opioid Receptor Expression after Morphine Administration Is Regulated by miR-212/132 Cluster

Authors

Garcia-Concejo, A., Jimenez-Gonzalez, A., Rodríguez, R.E.

ID

ZDB-PUB-170802-26

Date

2016

Source

PLoS One 11: e0157806 (Journal)

Registered Authors

Keywords

Morphine, MicroRNAs, Opioids, Embryos, 3' UTR, Zebrafish, MAPK signaling cascades, Neurons

MeSH Terms

Reverse Transcriptase Polymerase Chain Reaction
Immunohistochemistry
3' Untranslated Regions/genetics
Cells, Cultured
Zebrafish/embryology
Zebrafish/genetics*
Zebrafish/metabolism
Receptors, Opioid, mu/genetics*
Receptors, Opioid, mu/metabolism
Analgesics, Opioid/administration & dosage
Analgesics, Opioid/pharmacology
In Situ Hybridization
MicroRNAs/genetics*
Gene Knockdown Techniques
Gene Expression Regulation, Developmental/drug effects*
Animals
MAP Kinase Signaling System
Morphine/administration & dosage
Morphine/pharmacology*
Multigene Family
Time Factors
Cyclic AMP-Dependent Protein Kinases/metabolism
Zebrafish Proteins/genetics*
Zebrafish Proteins/metabolism
Methyl-CpG-Binding Protein 2/metabolism

(all 25)

PubMed

27380026 Full text @ PLoS One

Abstract

Since their discovery, miRNAs have emerged as a promising therapeutical approach in the treatment of several diseases, as demonstrated by miR-212 and its relation to addiction. Here we prove that the miR-212/132 cluster can be regulated by morphine, through the activation of mu opioid receptor (Oprm1). The molecular pathways triggered after morphine administration also induce changes in the levels of expression of oprm1. In addition, miR-212/132 cluster is actively repressing the expression of mu opioid receptor by targeting a sequence in the 3' UTR of its mRNA. These findings suggest that this cluster is closely related to opioid signaling, and function as a post-transcriptional regulator, modulating morphine response in a dose dependent manner. The regulation of miR-212/132 cluster expression is mediated by MAP kinase pathway, CaMKII-CaMKIV and PKA, through the phosphorylation of CREB. Moreover, the regulation of both oprm1 and of the cluster promoter is mediated by MeCP2, acting as a transcriptional repressor on methylated DNA after prolonged morphine administration. This mechanism explains the molecular signaling triggered by morphine as well as the regulation of the expression of the mu opioid receptor mediated by morphine and the implication of miR-212/132 in these processes.

Genes / Markers

Figures

Show all Figures

Expression

Gene	Antibody	Fish	Conditions	Stage	Anatomy	Assay	Figure
oprm1		AB	chemical treatment by environment: morphine	High-pec	whole organism	RTPCR	Fig. 2
oprm1		AB	standard conditions	High-pec	whole organism	RTPCR	Fig. 2
oprm1		AB	chemical treatment by environment: morphine	Prim-5	whole organism	RTPCR	Fig. 2
oprm1		AB	standard conditions	Prim-5	whole organism	RTPCR	Fig. 2
oprm1	Ab1-oprm1	AB	chemical treatment by environment: morphine	Prim-5	whole organism	WB	Fig. 2
oprm1		AB + MO1-dre-mir-212	chemical treatment by environment: morphine	Long-pec	whole organism	RTPCR	Fig. 2
oprm1		AB + MO1-dre-mir-212	chemical treatment by environment: morphine	Prim-5	whole organism	RTPCR	Fig. 2

1 - 7 of 7

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
AB	chemical treatment by environment: morphine	Prim-5	whole organism oprm1 expression increased amount, abnormal	Fig. 2
AB	chemical treatment by environment: morphine	Prim-5	whole organism oprm1 expression increased amount, abnormal	Fig. 2
AB	chemical treatment by environment: morphine	High-pec	whole organism oprm1 expression increased amount, abnormal	Fig. 2
AB + MO1-dre-mir-212	chemical treatment by environment: morphine	Prim-5	whole organism oprm1 expression increased amount, abnormal	Fig. 2
AB + MO1-dre-mir-212	chemical treatment by environment: morphine	Long-pec	whole organism oprm1 expression increased amount, abnormal	Fig. 2

1 - 5 of 5

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Mutations / Transgenics

Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
dre-mir-132-1	MO3-dre-mir-132-1	MRPHLNO
dre-mir-212	MO1-dre-mir-212	MRPHLNO
oprm1	MO1-oprm1	MRPHLNO

Fish

Fish
AB
AB + MO1-dre-mir-212
AB + MO3-dre-mir-132-1

Antibodies

Name	Type	Antigen Genes	Isotypes	Host Organism
Ab1-oprm1		oprm1		Rabbit

Orthology

Engineered Foreign Genes

Mapping

Garcia-Concejo et al., 2016 ZDB-PUB-170802-26 PMID:27380026

μ Opioid Receptor Expression after Morphine Administration Is Regulated by miR-212/132 Cluster

Garcia-Concejo et al., 2016

ZDB-PUB-170802-26
PMID:27380026