Abstract
Circular RNA (circRNA), a novel type of endogenous non-coding RNA, plays natural miRNA sponge effect that represses the activities of corresponding miRNAs through binding with them, thus modulating transcriptional expression of genes. Recent studies indicate that circRNAs are significantly enriched in the brain and some of them are derived from synaptic protein-coding genes. In addition, miRNAs are involved in synaptic plasticity, memory formation, and cocaine addiction. However, the role of circRNAs in cocaine reward is unclear. This study aimed to investigate the expression profile of striatal circRNAs in the mice after cocaine self-administration. By using circRNA microarray analysis, we observed that 90 striatal circRNAs were differentially expressed in cocaine self-administering mice, of which 18 circRNAs were up-regulated and 72 down-regulated. Six circRNAs were selected randomly for validation by using quantitative reverse transcription-PCR, and their expression levels showed consistency with microarray analysis. We backward predicted the circRNAs and their binding sites of miRNAs associated with neuroplasticity. In functional validation test, mmu_circRNA_002381 may modulate the transcription of certain genes associated with neuroplasticity, such as limk1 and bdnf. Taken together, circRNAs may participate in cocaine behavioral effect via interacting with miRNAs. Our findings reveal a potential role of circRNAs in cocaine effect.
Highlights
It has been known that cocaine epigenetically alters the expression of genes and miRNAs through histone tail or DNA modification in brain’s reward circuitry[1,2,3]
CircRNA is a novel type of non-coding RNA, which is involved in various biological functions[8]
We aimed to investigate the potential role of striatal circRNAs in cocaine reward
Summary
It has been known that cocaine epigenetically alters the expression of genes and miRNAs through histone tail or DNA modification in brain’s reward circuitry[1,2,3]. Striatal miRNA plays a vital role in memory, neuroplasticity, and rewarding effect[3,4]. Striatal miR-212 represses the compulsive drug-taking behavior, and modulates the neuroplasticity to cocaine addiction[5,6,7]. Through interplaying with striatal miR-212, MeCP2 regulates the expression of brain-derived neurotrophic factor (BDNF) and cocaine intake[6]. CircRNA is a novel type of non-coding RNA, which is involved in various biological functions[8]. CircRNAs are typically generated through a process of back-splicing from exons and a covalent bond linking the 3′- and 5′-end[9,10]
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