Opioids, primarily used for pain relief, are still nowadays the preferred analgesics for the treatment of chronic pain. Among them, morphine is the most used molecule, although it is well known for inducing the appearance of tolerance and addiction after prolonged administration. This opiate binds to the mu opioid receptor (Oprm1) with the highest affinity and, therefore, the effects of this drug, especially in the central nervous system (CNS), are mediated by the activation of this receptor (Pert et al., 1987). Opioid receptors are G-protein coupled receptors and the signaling cascade triggered by them induces the activity of several transcription factors, including cAMP Response Element Binding (CREB) protein (Impey et al., 2004; Ma et al., 2001), a transcription factor involved in many molecular pathways by controlling the transcription of different genes. Morphine also alters calcium and potassium signaling and controls PKA activity by the inhibition of adenylate cyclase (AC); in this way it also induces changes in gene expression in the target cell (Kumar et al., 2010). It is also known that morphine regulates nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kß) activation through IP3/Akt pathway, although the molecular mechanism implicated in this situation still remains uncharacterized (Chen et al., 2006). equal (Mohammed et al., 2014), indicating that the process of splicing is not only a maturation process but also a regulatory mechanism that controls the expression of each of the mature miRNAs. After the pri-miRNA has been transcribed, it is cleaved by several processing enzymes such as Dicer, leading to a shorter hairpin-like structured named precursor miRNA (pre-miRNA). After this processing, pre-miRNAs are transported into the cytoplasm by exportin-5 and they suffer another splicing by the processing enzyme Drosha. After this process, two mature miRNAs are generated. In general terms, only one of these two miRNAs exert its function, although several cases have been described in which both molecules may have their own regulatory roles. These molecules control gene expression by binding to complementary sequences in the 3′ untranslated region (3′ UTR) of their target mRNA transcripts to facilitate their degradation and/or inhibit their translation (Bartel, 2009), although binding to other regions have been described (Doench and Sharp, 2004; Greco and Rameshwar, 2007). miRNAs are involved in many developmental processes, such as differentiation and proliferation and their dysregulation has been linked to a wide variety of diseases (Sidhu regulation of myoblasts proliferation and differentiation in part by regulating the YY1-miR-29 negative regulatory circuit. Developmental changes and cell type-specific distribution of miR-29 expression, such as that reported in the murine lung (Cushing et al., 2011), further support the presence of dynamic regulation of the expression of miR-29. miR-29a has also been shown to regulate the expression of ADAM12 expression by binding to the 3'UTR region ...
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