Regulation of Opioid Tolerance by let-7 Family MicroRNA Targeting the μ Opioid Receptor

Hé, Ying; Yang, Cheng; Kirkmire, Chelsea M.; Wang, Zaijie Jim

doi:10.1523/jneurosci.2419-10.2010

Cited by 177 publications

(159 citation statements)

References 40 publications

(51 reference statements)

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“…These data suggest a potential role for microRNAs in the regulation of alternatively spliced mRNA in drug addiction and abuse. Additionally, miRNAs-mediated mechanisms were also involved in opioid addiction, such as miR-23b, let-7, and miR-190 (Wu et al 2008;He et al 2010;Zheng et al 2010). Overall, these studies support a role for miRNAs in already highly sophisticated molecular mechanisms of addiction, and advocate further research in this field.…”

Section: Micrornas In Drug Addictionmentioning

confidence: 55%

MicroRNAs in learning, memory, and neurological diseases: Figure 1.

2012

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MicroRNAs (miRNAs) represent a class of small regulatory noncoding RNAs 22 bp in length that mediate post-transcriptional silencing of gene expression via the recognition of specific sequences in target messenger (m)RNAs. The current body of literature suggests that miRNAs are fine-tuning regulators of gene expression profiles in a wide range of biological processes, from development to cancer. Many miRNAs are highly expressed in the adult nervous system in a spatially and temporally controlled manner in normal physiology, as well as in certain pathological conditions. These findings emphasize that gene regulation networks based on miRNA activities may be particularly important to brain function, and that perturbation of these networks may result in abnormal brain function. Indeed, miRNAs have been implicated in various aspects of dendrite remodeling and synaptic plasticity, as well as in experience-dependent adaptive changes of neural circuits in the postnatal developmental and adult brain. Recent advances in methods of next-generation sequencing, such as RNA-seq, offer the means to quantitatively evaluate the functions of miRNAs in a genome-wide manner in large cohorts of samples. These new technologies have already yielded valuable information and are expanding our understanding of miRNA-based mechanisms in higher-order brain processing, including learning and memory and cognition, as well as in neuropsychiatric disorders.

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Section: Micrornas In Drug Addictionmentioning

confidence: 55%

MicroRNAs in learning, memory, and neurological diseases: Figure 1.

2012

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“…Mu opioids such as morphine modulate expression of a number of miRNAs (Sanchez-Simon et al, 2010;Zheng et al, 2010;Wu et al, 2008Wu et al, , 2013Dave and Khalili, 2010;He et al, 2010;Wang et al, 2011), and several miRNAs regulate MOR-1 expression (Wu et al, 2008(Wu et al, , 2009He et al, 2010). Dysregulation of miRNAs has been linked to morphine tolerance and addiction Dreyer, 2010;Hwang et al, 2012;Tapocik et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Morphine Regulates Expression ofμ-Opioid Receptor MOR-1A, an Intron-Retention Carboxyl Terminal Splice Variant of theμ-Opioid Receptor (OPRM1) Gene via miR-103/miR-107

et al. 2013

Mol Pharmacol

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The m-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 m agonists such as morphine modulate miRNA expression. However, little is known about miRNA regulation of the OPRM1 splice variants. Using 39-rapid amplification cDNA end and Northern blot analyses, we identified the complete 39-untranslated region (39-UTR) for both mouse and human MOR-1A and their conserved polyadenylation site, and defined the role the 39-UTR in mRNA stability using a luciferase reporter assay. Computer models predicted a conserved miR-103/107 targeting site in the 39-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 39-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 morphinetolerant 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.

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“…miRNAs have been implicated in mediating the effects of cocaine (8,9,18,22), nicotine (19,20), alcohol (41,44), and several other classes of drugs of abuse (17,33,67). In the case of cocaine addiction in rats, the upregulation of miR-181a and the downregulation of two other miRNAs, let-7d and miR124a, has been revealed in addiction-relevant regions of the brain (8).…”

mentioning

confidence: 99%

Dopamine-Regulated MicroRNA MiR-181a Controls GluA2 Surface Expression in Hippocampal Neurons

Saba

Störchel

Aksoy‐Aksel

et al. 2012

Molecular and Cellular Biology

194

172

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The dynamic expression of AMPA-type glutamate receptors (AMPA-R) at synapses is a key determinant of synaptic plasticity, including neuroadaptations to drugs of abuse. Recently, microRNAs (miRNAs) have emerged as important posttranscriptional regulators of synaptic plasticity, but whether they target glutamate receptors to mediate this effect is not known. Here we used microarray screening to identify miRNAs that regulate synaptic plasticity within the nucleus accumbens, a brain region critical to forming drug-seeking habits. One of the miRNAs that showed a robust enrichment at medium spiny neuron synapses was miR-181a. Using bioinformatics tools, we detected a highly conserved miR-181a binding site within the mRNA encoding the GluA2 subunit of AMPA-Rs. Overexpression and knockdown of miR-181a in primary neurons demonstrated that this miRNA is a negative posttranscriptional regulator of GluA2 expression. Additionally, miR-181a overexpression reduced GluA2 surface expression, spine formation, and miniature excitatory postsynaptic current (mEPSC) frequency in hippocampal neurons, suggesting that miR-181a could regulate synaptic function. Moreover, miR-181a expression was induced by dopamine signaling in primary neurons, as well as by cocaine and amphetamines, in a mouse model of chronic drug treatment. Taken together, our results identify miR-181a as a key regulator of mammalian AMPA-type glutamate receptors, with potential implications for the regulation of drug-induced synaptic plasticity.

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Regulation of Opioid Tolerance by let-7 Family MicroRNA Targeting the μ Opioid Receptor

Cited by 177 publications

References 40 publications

MicroRNAs in learning, memory, and neurological diseases: Figure 1.

MicroRNAs in learning, memory, and neurological diseases: Figure 1.

Morphine Regulates Expression ofμ-Opioid Receptor MOR-1A, an Intron-Retention Carboxyl Terminal Splice Variant of theμ-Opioid Receptor (OPRM1) Gene via miR-103/miR-107

Dopamine-Regulated MicroRNA MiR-181a Controls GluA2 Surface Expression in Hippocampal Neurons

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