Abstract:Natural antisense transcripts (NATs) are an abundant class of long noncoding RNAs that have recently been shown to be key regulators of chromatin dynamics and gene expression in nervous system development and neurological disorders. However, it is currently unclear if NAT-based mechanisms also play a role in drug-induced neuroadaptations. Aberrant regulation of gene expression is one critical factor underlying the long-lasting behavioral abnormalities that characterize substance use disorder, and it is possibl… Show more
“…We firstly identified DElncRNAs, DEmiRNAs and DEmRNAs in morphine addiction. Although these lncRNAs have not been reported to be involved in drug addiction, dysregulated expression of lncRNAs has been reported to play a critical role in the progression of addiction ( 26 , 27 ). Gao et al showed that upregulation of MEG3 was involved in morphine-induced autophagy in hippocampal neuronal HT22 cells ( 28 ).…”
Recent research suggest that some non-coding RNAs (ncRNAs) are important regulators of chromatin dynamics and gene expression in nervous system development and neurological diseases. Nevertheless, the molecular mechanisms of long non-coding RNAs (lncRNAs), acting as competing endogenous RNAs (ceRNAs), underlying morphine addiction are still unknown. In this research, RNA sequencing (RNA-seq) was used to examine the expression profiles of lncRNAs, miRNAs and mRNAs on the nucleus accumbens (NAc) tissues of mice trained with morphine or saline conditioned place preference (CPP), with differential expression of 31 lncRNAs, 393 miRNAs, and 371 mRNAs found. A ceRNA network was established for reciprocal interactions for 9 differentially expressed lncRNAs (DElncRNAs), 10 differentially expressed miRNAs (DEmiRNAs) and 12 differentially expressed mRNAs (DEmRNAs) based on predicted miRNAs shared by lncRNAs and mRNAs. KEGG pathway enrichment analyses were conducted to explore the potential functions of DEmRNAs interacting with lncRNAs in the ceRNA network. These DEmRNAs were enriched in synaptic plasticity-related pathways, including pyrimidine metabolism, ECM-receptor interaction, and focal adhesion. The correlation between the relative expression of lncRNAs, miRNAs and mRNAs was analyzed to further validate predicted ceRNA networks, and the Lnc15qD3-miR-139-3p-Lrp2 ceRNA regulatory interaction was determined. These results suggest that the comprehensive network represents a new insight into the lncRNA-mediated ceRNA regulatory mechanisms underlying morphine addiction and provide new potential diagnostic and prognostic biomarkers for morphine addiction.
“…We firstly identified DElncRNAs, DEmiRNAs and DEmRNAs in morphine addiction. Although these lncRNAs have not been reported to be involved in drug addiction, dysregulated expression of lncRNAs has been reported to play a critical role in the progression of addiction ( 26 , 27 ). Gao et al showed that upregulation of MEG3 was involved in morphine-induced autophagy in hippocampal neuronal HT22 cells ( 28 ).…”
Recent research suggest that some non-coding RNAs (ncRNAs) are important regulators of chromatin dynamics and gene expression in nervous system development and neurological diseases. Nevertheless, the molecular mechanisms of long non-coding RNAs (lncRNAs), acting as competing endogenous RNAs (ceRNAs), underlying morphine addiction are still unknown. In this research, RNA sequencing (RNA-seq) was used to examine the expression profiles of lncRNAs, miRNAs and mRNAs on the nucleus accumbens (NAc) tissues of mice trained with morphine or saline conditioned place preference (CPP), with differential expression of 31 lncRNAs, 393 miRNAs, and 371 mRNAs found. A ceRNA network was established for reciprocal interactions for 9 differentially expressed lncRNAs (DElncRNAs), 10 differentially expressed miRNAs (DEmiRNAs) and 12 differentially expressed mRNAs (DEmRNAs) based on predicted miRNAs shared by lncRNAs and mRNAs. KEGG pathway enrichment analyses were conducted to explore the potential functions of DEmRNAs interacting with lncRNAs in the ceRNA network. These DEmRNAs were enriched in synaptic plasticity-related pathways, including pyrimidine metabolism, ECM-receptor interaction, and focal adhesion. The correlation between the relative expression of lncRNAs, miRNAs and mRNAs was analyzed to further validate predicted ceRNA networks, and the Lnc15qD3-miR-139-3p-Lrp2 ceRNA regulatory interaction was determined. These results suggest that the comprehensive network represents a new insight into the lncRNA-mediated ceRNA regulatory mechanisms underlying morphine addiction and provide new potential diagnostic and prognostic biomarkers for morphine addiction.
“…However, a study revealed an increase in the expression of HOTAIRM1 in differentiating neurons, suggesting a role in early neurogenesis and brain development that may be disrupted by prenatal cocaine exposure (Lin et al, 2011). Another transcriptomic study also found an increase in Homer1 antisense (Homer1-AS) in the nucleus accumbens of mice after repeated cocaine exposure that in vitro was demonstrated to increase Homer1 sense expression (Sartor et al, 2017). Homer1 is an immediate-early gene and a scaffold protein found in postsynaptic densities that is associated with plasticity and spine morphogenesis (Shiraishi-Yamaguchi & Furuichi, 2007), meaning abnormal expression of Homer1-AS and subsequent dysregulation of Homer1 as a result of prenatal cocaine exposure may contribute to some of the abnormal neural development associated with prenatal cocaine exposure.…”
Completion of the Human Genome Project has led to the identification of a large number of transcription start sites that are not paired with protein‐coding genes, supporting the growing recognition of the abundance of encoded nonprotein‐coding RNAs (ncRNAs) and their importance for speciation and species‐specific development. Present in both plants and animals, ncRNAs vary in size, function, primary sequence, and secondary structure. While microRNAs (miRNAs) are the best known, there are a number of other ncRNAs (long[er] nonprotein‐coding RNA, pseudogenes, circular RNAs, and so on) that have been shown to play an important role in the development either directly or via networks of proteins and other ncRNAs, including modulating the impact of miRNAs. Furthermore, these ncRNAs and their developmental regulatory networks are sensitive to teratogens such as ethanol, cannabis, cocaine, and nicotine. A better understanding of the developmental role of ncRNAs and their capacity to mediate teratogenesis is a necessary step in efforts to minimize the long‐term consequences of developmental exposures to drugs‐of‐abuse. Moreover, with increasing awareness of the prevalence of polydrug use, experimental models will need to incorporate more complex drug exposure paradigms into meaningful assessments of developmental ncRNA function.
“…Additionally, they found evidence that these corresponding changes in NAc lncRNA might correspond with changes in addiction-associated mRNA ( Zhu et al, 2016 ). Further research has characterized a specific lncRNA that is antisense to a synaptically localized addiction-related gene, Homer1 ( Sartor et al, 2017 ). After repeated injections of cocaine, it was found that Homer1-AS was increased within the NAc.…”
Section: Ncrna Regulation Of Substance Use Disorders (Suds)mentioning
The discovery of non-coding RNAs (ncRNAs)has been one of the central findings from early genomic sequencing studies. Not only was the presence of these genes unknown previously, it was the staggering disproportionate share of the genome that was predicted to be encoded by ncRNAs that was truly significant in genomic research. Over the years the function of various classes of these ncRNAs has been revealed. One of the first and enduring regulatory programs associated with these factors was development. In the neurosciences, the discovery of adult derived populations of dividing cells within the brain was equally substantial. The brain was hypothesized to be plastic only in its neuronal connectivity, but the discovery of the generation of new neurons was a novel mechanism of neuronal and behavioral plasticity. The process of adult neurogenesis resembles early neuronal development and has been found to share many parallels in the proper stages of specified genetic programs. Adult neurogenesis has also been found to play a role in learning and memory involved in particular hippocampal-dependent behaviors. Substance use disorders (SUDs) are an example of a behavioral condition that is associated with and possibly driven by hippocampal alterations. Our laboratory has determined that hippocampal adult neurogenesis is necessary for a rodent model of methamphetamine relapse. Due to the previous research on ncRNAs in development and in other brain regions involved in SUDs, we posit that ncRNAs may play a role in adult neurogenesis associated with this disorder. This review will cover the regulatory mechanisms of various classes of ncRNAs on the coordinated genetic program associated with adult neurogenesis with a special focus on how these programs could be dysregulated in SUDs.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.