GeneSet Information

Tier III GS400152 • Downregulated lncRNAs in the ventral midbrain of humans with a history of chronic cocaine use (microarray)

DESCRIPTION:

Long noncoding RNAs (lncRNAs) that are downregulated in the ventral midbrain of human subjects with cocaine addiction. Post-mortem human ventral midbrain samples were collected, and lncRNA expression was evaluated via microarray analysis. Data taken from Table 2. Values presented are average fold difference. Data available from GEO with accession number GSE67281."

LABEL:

downreg lncRNAs cocaine human

SCORE TYPE:

Effect

DATE ADDED:

2021-06-28

DATE UPDATED:

2024-04-25

SPECIES:

AUTHORS:

Michael J Bannon, Candace L Savonen, Hui Jia, Fabien Dachet, Steven D Halter, Carl J Schmidt, Leonard Lipovich, Gregory Kapatos

TITLE:

Identification of long noncoding RNAs dysregulated in the midbrain of human cocaine abusers.

JOURNAL:

Journal of neurochemistry Oct 2015, Vol 135, pp. 50-9

ABSTRACT:

Maintenance of the drug-addicted state is thought to involve changes in gene expression in different neuronal cell types and neural circuits. Midbrain dopamine (DA) neurons in particular mediate numerous responses to drugs of abuse. Long noncoding RNAs (lncRNAs) regulate CNS gene expression through a variety of mechanisms, but next to nothing is known about their role in drug abuse. The proportion of lncRNAs that are primate-specific provides a strong rationale for their study in human drug abusers. In this study, we determined a profile of dysregulated putative lncRNAs through the analysis of postmortem human midbrain specimens from chronic cocaine abusers and well-matched control subjects (n = 11 in each group) using a custom lncRNA microarray. A dataset comprising 32 well-annotated lncRNAs with independent evidence of brain expression and robust differential expression in cocaine abusers is presented. For a subset of these lncRNAs, differential expression was validated by quantitative real-time PCR and cellular localization determined by in situ hybridization histochemistry. Examples of lncRNAs exhibiting DA cell-specific expression, different subcellular distributions, and covariance of expression with known cocaine-regulated protein-coding genes were identified. These findings implicate lncRNAs in the cellular responses of human DA neurons to chronic cocaine abuse. Long noncoding RNAs (lncRNAs) regulate the expression of protein-coding genes, but little is known about their potential role in drug abuse. In this study, we identified lncRNAs differentially expressed in human cocaine abusers' midbrains. One up-regulated antisense lncRNA, tumor necrosis factor receptor-associated factor 3-interacting protein 2-antisense 1 (TRAF3IP2-AS1), was found predominantly in the nucleus of human dopamine (DA) neurons, whereas the related TRAF3IP2 protein-coding transcript was distributed throughout these cells. The abundances of these transcripts were significantly correlated (left) suggesting that TRAF3IP2-AS1 may regulate TRAF3IP2 gene expression, perhaps through local chromatin changes at this locus (right). PUBMED: 26222413
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response to cocaine trait (VT:0010718)
response to addictive substance trait (VT:0010488)
response to xenobiotic stimulus trait (VT:0010487)
organism trait (VT:0010454)

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