Long-Term Morphine Treatment Decreases the Association of μ-Opioid Receptor (MOR1) mRNA with Polysomes through miRNA23b

Abstract

ABSTRACT-Opioid receptor (MOR) mediates most of the pharmacological effects of opioid drugs. The expression of MOR is temporarily and spatially regulated at both the transcriptional and post-transcriptional levels. Long-term morphine treatment that induces tolerance does not alter MOR mRNA expression, suggesting no direct link between agonist treatment and MOR gene transcription. We previously identified the 3Ј-untranslated region (3Ј-UTR) of the major transcript of -opioid receptor (MOR1) and revealed a novel trans-acting factor, miRNA23b, that binds to the K box motif in the 3Ј-UTR. The interaction between miRNA23b with the MOR1 3Ј-UTR suppressed receptor translation by inhibiting polysome-mRNA association. In this report, we demonstrate that long-term morphine treatment increases miRNA23b expression in a dose-and time-dependent manner and represses the association of MOR1 mRNA with polysomes through the MOR1 3Ј-UTR. The translational luciferase reporter assay shows a suppression effect of morphine on reporter activity that requires the MOR1 3Ј-UTR. This suggests a potential link between MOR expression and morphine treatment at the post-transcriptional level in which a specific miRNA, miRNA23b, is involved.

Do Opioids Activate Latent HIV-1 by Down-Regulating Anti-HIV microRNAs?

“…Increasing evidence suggests that morphine treatment can modulate the expression of various miRNAs (Wu et al 2009;Dave and Khalili 2010;Sanchez-Simon et al 2010). Since morphine down regulates the expression of anti-HIV miRNAs in monocytes in vitro and heroin addicts have lower levels of these miRNAs in PBMCs (Wang et al 2011), and down-regulation of these miRNAs can promote replication of latent HIV-1 in resting CD4+ T cells (Huang et al 2007) and in monocytes (Wang et al 2009) …”

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

“…We further illustrated that miR-103/107 mainly functions at the post-transcriptional or translational level to regulate MOR-1A expression, as shown by the increase in polyribosomeassociated MOR-1A mRNA when the mutant construct and miR-107 inhibitor were used, without affecting steady-state mRNA levels. Previous studies indicated that several miRNAs such as miR-23b and let-7 inhibit the expression of the original mMOR-1 at the post-transcriptional level through their binding sites located at the 39-UTR (Wu et al, 2008(Wu et al, , 2009He et al, 2010). Our study shows for the first time that a pair of paralogous miRNAs, miR-103 and miR-107, can regulate the expression of a C-terminal splice variant at the post-transcriptional level through its 39-UTR, as determined by measurement of polyribosome-associated mRNA.…”

“…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).…”

mRNA changes in nucleus accumbens related to methamphetamine addiction in mice

“…Previous findings demonstrated miRNAs as significant modulators in controlling the impacts of abused drugs such as cocaine, nicotine, morphine and opioids, on brain rewarding circuits and the development of addiction-related behaviors678910. LncRNAs are known to control genes expression through various mechanisms and are likely to influence brain development, neuronal plasticity, and neural disease1112131415.…”