MicroRNAs in Opioid Pharmacology

Hwang, Cheol Kyu; Wagley, Yadav; Law, Ping Yee; Li, Wei; Loh, Horace H.

doi:10.1007/s11481-011-9323-2

Cited by 39 publications

(35 citation statements)

References 113 publications

(151 reference statements)

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“…At least 35 up-regulated miRNAs have been found to take part in alcohol-induced effects by regulating mechanisms such as the cell cycle and apoptosis [160], and 11 miRNAs were reported to play regulatory roles in opioid pharmacology [161]. However, only a few miRNAs have been shown to participate in the effects of addictive drugs on adult NSPCs by interacting with other mechanisms.…”

Section: Common Mechanisms In Adult Nspc Regulationmentioning

confidence: 99%

Effects of addictive drugs on adult neural stem/progenitor cells

Loh

Law

2015

Cell. Mol. Life Sci.

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Neural stem/progenitor cells (NSPCs) undergo a series of developmental processes before giving rise to newborn neurons, astrocytes and oligodendrocytes in adult neurogenesis. During the past decade, the role of NSPCs has been highlighted by studies on adult neurogenesis modulated by addictive drugs. It has been proven that these drugs regulate the proliferation, differentiation and survival of adult NSPCs in different manners, which results in the varying consequences of adult neurogenesis. The effects of addictive drugs on NSPCs are exerted via a variety of different mechanisms and pathways, which interact with one another and contribute to the complexity of NSPC regulation. Here, we review the effects of different addictive drugs on NSPCs, and the related experimental methods and paradigms. We also discuss the current understanding of major signaling molecules, especially the putative common mechanisms, underlying such effects. Finally, we review the future directions of research in this area.

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Section: Common Mechanisms In Adult Nspc Regulationmentioning

confidence: 99%

Effects of addictive drugs on adult neural stem/progenitor cells

Loh

Law

2015

Cell. Mol. Life Sci.

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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). Yet there has been a lack of information regarding miRNA Fig.…”

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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“…We have previously identified trans-acting factors, such as miR-23b and miR-339, that suppress translation of MOR mRNA through its own 3′-UTR (Wu et al, 2008, 2013; Hwang et al, 2012). Others have also found a trans-acting miRNA, let-7, that interacts with its binding site in the MOR 3′-UTR and suppresses MOR translation (He et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

“…Recent reports indicate that microRNAs regulate the MOR gene by binding to target sites in the 3′-UTR of MOR (Hwang et al, 2012). Opioids increased the expression of three microRNAs, miR-23b (Wu et al, 2009), let-7 (He et al, 2010), and miR-339-3p (Wu et al, 2013), resulting in downregulation of the MOR gene at the post-transcriptional level.…”

Section: Introductionmentioning

confidence: 99%

Phosphorylation of poly(rC) binding protein 1 (PCBP1) contributes to stabilization of mu opioid receptor (MOR) mRNA via interaction with AU-rich element RNA-binding protein 1 (AUF1) and poly A binding protein (PABP)

Hwang

Wagley

Law

et al. 2017

Gene

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Gene regulation at the post-transcriptional level is frequently based on cis- and trans-acting factors on target mRNAs. We found a C-rich element (CRE) in mu-opioid receptor (MOR) 3′-untranslated region (UTR) to which poly (rC) binding protein 1 (PCBP1) binds, resulting in MOR mRNA stabilization. RNA immunoprecipitation and RNA EMSA revealed the formation of PCBP1-RNA complexes at the element. Knockdown of PCBP1 decreased MOR mRNA half-life and protein expression. Stimulation by forskolin increased cytoplasmic localization of PCBP1 and PCBP1/MOR 3′-UTR interactions via increased serine phosphorylation that was blocked by protein kinase A (PKA) or (phosphatidyl inositol-3) PI3-kinase inhibitors. The forskolin treatment also enhanced serine- and tyrosine-phosphorylation of AU-rich element binding protein (AUF1), concurrent with its increased binding to the CRE, and led to an increased interaction of poly A binding protein (PABP) with the CRE and poly(A) sites. AUF1 phosphorylation also led to an increased interaction with PCBP1. These findings suggest that a single co-regulator, PCBP1, plays a crucial role in stabilizing MOR mRNA, and is induced by PKA signaling by conforming to AUF1 and PABP.

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MicroRNAs in Opioid Pharmacology

Cited by 39 publications

References 113 publications

Effects of addictive drugs on adult neural stem/progenitor cells

Effects of addictive drugs on adult neural stem/progenitor cells

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

Phosphorylation of poly(rC) binding protein 1 (PCBP1) contributes to stabilization of mu opioid receptor (MOR) mRNA via interaction with AU-rich element RNA-binding protein 1 (AUF1) and poly A binding protein (PABP)

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