Abstract

BACKGROUND: We previously discovered that 3 long non-coding RNAs (lncRNAs) NONHSAT089447, NONHSAT021545, and NONHSAT041499 were differentially expressed in the peripheral blood of patients with schizophrenia, in comparison to those in normal healthy controls. In this study, we conducted bioinformatic analysis of these 3 lncRNAs and the regulatory role of lncRNA NONHSAT089447 in the dopamine signaling pathway in patients with schizophrenia.

MATERIAL AND METHODS: There lncRNAs in peripheral blood mononuclear cells (PBMCs) were screened using microarray analysis. Pearson’s correlation analysis was performed to assess the levels of co-expressed mRNAs of respective lncRNAs. The Database for Annotation, Visualization and Integrated Discovery (DAVID) software was used to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes or Genomes (KEGG) enrichment analysis for these lncRNAs. Human neuroblastoma cell lines (SK-N-SH) were cultured and treated with dopamine or olanzapine (OLP), or transfected with siRNA targeting NONHSAT089447 or plasmid expressing NONHSAT089447. Levels of lncRNAs were detected by quantitative real-time reverse transcription polymerase chain reaction (RT-PCR). Then, mRNA and protein expression of the dopamine receptors DRD1, DRD2, DRD3, DRD4, and DRD5 were measured by RT-PCR and western blot analysis, respectively.

RESULTS: OLP treatment significantly inhibited the expression of NONHSAT089447. Knockdown of NONHSAT089447 by siRNA decreased DRD3 and DRD5 expression, while overexpression of NONHSAT089447 significantly upregulated expression of DRD3 and DRD5. Western blot analysis confirmed that levels of NONHSAT089447 regulated downstream DRD signaling.

CONCLUSIONS: Our results revealed that the lncRNA NONHSAT089447 participated in the dopamine signaling pathway via upregulation of DRDs.

Keywords: Dopamine, Neuroblastoma, RNA, Long Noncoding, Schizophrenia, Anxiety Disorders, Computational Biology, Depressive Disorder, Major, Gene Expression Profiling, gene ontology, Oligonucleotide Array Sequence Analysis, RNA, Messenger, Real-Time Polymerase Chain Reaction