μ Opioid Receptor Expression after Morphine Administration Is Regulated by miR-212/132 Cluster.
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 (Oprm...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2016-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4933400?pdf=render |
| _version_ | 1811233195120656384 |
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| author | Adrian Garcia-Concejo Ada Jimenez-Gonzalez Raquel E Rodríguez |
| author_facet | Adrian Garcia-Concejo Ada Jimenez-Gonzalez Raquel E Rodríguez |
| author_sort | Adrian Garcia-Concejo |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T11:17:35Z |
| format | Article |
| id | doaj.art-1f64343f43b14c06bef4c51e96d556b1 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T11:17:35Z |
| publishDate | 2016-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-1f64343f43b14c06bef4c51e96d556b12022-12-22T03:35:28ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01117e015780610.1371/journal.pone.0157806μ Opioid Receptor Expression after Morphine Administration Is Regulated by miR-212/132 Cluster.Adrian Garcia-ConcejoAda Jimenez-GonzalezRaquel E RodríguezSince 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.http://europepmc.org/articles/PMC4933400?pdf=render |
| spellingShingle | Adrian Garcia-Concejo Ada Jimenez-Gonzalez Raquel E Rodríguez μ Opioid Receptor Expression after Morphine Administration Is Regulated by miR-212/132 Cluster. PLoS ONE |
| title | μ Opioid Receptor Expression after Morphine Administration Is Regulated by miR-212/132 Cluster. |
| title_full | μ Opioid Receptor Expression after Morphine Administration Is Regulated by miR-212/132 Cluster. |
| title_fullStr | μ Opioid Receptor Expression after Morphine Administration Is Regulated by miR-212/132 Cluster. |
| title_full_unstemmed | μ Opioid Receptor Expression after Morphine Administration Is Regulated by miR-212/132 Cluster. |
| title_short | μ Opioid Receptor Expression after Morphine Administration Is Regulated by miR-212/132 Cluster. |
| title_sort | μ opioid receptor expression after morphine administration is regulated by mir 212 132 cluster |
| url | http://europepmc.org/articles/PMC4933400?pdf=render |
| work_keys_str_mv | AT adriangarciaconcejo mopioidreceptorexpressionaftermorphineadministrationisregulatedbymir212132cluster AT adajimenezgonzalez mopioidreceptorexpressionaftermorphineadministrationisregulatedbymir212132cluster AT raquelerodriguez mopioidreceptorexpressionaftermorphineadministrationisregulatedbymir212132cluster |