MicroRNAs (miRNAs) are small non-coding RNAs that function as translational
repressors and represent an important element in tissue development as well as disease. MiRNA
sequences and their target sites in mRNAs show an extensive degree of conservation across
species. A single miRNA is now believed to recognize the 3’untranslated region of mRNAs in a
sequence-specific manner to inhibit the protein expression of literally hundreds of targeted
mRNAs. The human genome encodes more than 1000 miRNAs which target over 60% of
mammalian and human transcripts. It is thus not surprising that expression changes in miRNAs
can have a far-reaching impact on cellular functions, including the opioid system. Opioids,
psychoactive chemicals that resemble morphine in their pharmacological effects are a class of
potent analgesics used for treating various forms of acute and chronic pain. The mu opioid
receptor is primarily responsible for opioid analgesia and anti-nociceptive tolerance. There is an ever-growing
appreciation of miRNAs as important regulators of biological processes where opioids have an important impact, such as
regulation of opioid receptors themselves. For example, a large number of splice variants of the primary transcript involve
both 3' and 5' splicing of the mu opioid receptor mRNA, many of which can potentially be targeted by miRNAs.
Conversely, miRNAs can be regulated by opioids. Two mu opioid receptor agonists, morphine and fentanyl, display
differential mechanisms of signalling linked to specific miRNA expression. Moreover, miRNA – opioid connections
impact on neuronal cell development, drug addiction, pain perception, neuroimmune system interaction and cell
proliferation and tumorigenesis. These aspects will be the subject of this review.
Keywords: Addiction, fentanyl, microRNAs, morphine, mu opioid receptor, opioids, signal transduction, tolerance.
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