Analysis of the Effect of Chronic Morphine Treatment on miRNA Profile and Introduction of the MAPK Pathway as the Target of Differentially Expressed miRNAs

Different signaling pathways have been identified that are involved in the cellular response to opiates. The mitogen-activated protein kinase pathway is one of the most important signaling pathways underlying the neuronal response to opiates. MicroRNAs (miRNAs) are considered to be post-transcriptional regulators of gene expression with paramount significance, which plays key roles in modulating cellular processes such as neuronal plasticity and synaptic consolidation. The purpose of this study is to identify miRNAs that are differentially expressed in response to chronic morphine treatment, and predict those genes that have a possible role in this process. Because the MAPK pathway in involved in morphine dependence and participates in hypersensitivity to pain, determining miRNAs that modulate this pathway could be insightful in morphine dependence treatment and pain control.

In this study, the BE(2)-C neuroblastoma cell line was chronically treated with morphine sulphate and the changes in expression of 750 miRNAs were analyzed by real time PCR.

Two up- and down- regulated groups of miRNAs were determined to be differentially expressed in response to morphine: i) has-mir-193a-3p, -212, -181c, -362-3p, -639, -646 and ii) has-mir-412, -937, -558, -552, -943, -628-5p, -593, -555, -636, -643, 566, -571, -642, -653, -611, -31, let7-g.

The analysis of differentially expressed miRNAs showed that the MAPK signaling pathway could be regarded as a signaling pathway with utmost significance in chronic morphine response. Due to the role played by MAPK pathway in cellular response to morphine exposure, we can propose that protein phosphorylation has a presumable part in this response.