Abstract
Schizophrenia (SZ) and bipolar disorder (BD) are severe neuropsychiatric disorders with serious impact on patients, together termed “major psychosis”. Recently, long intergenic non-coding RNAs (lincRNAs) were reported to play important roles in mental diseases. However, little was known about their molecular mechanism in pathogenesis of SZ and BD. Here, we performed RNA sequencing on 82 post-mortem brain tissues from three brain regions (orbitofrontal cortex (BA11), anterior cingulate cortex (BA24) and dorsolateral prefrontal cortex (BA9)) of patients with SZ and BD and control subjects, generating over one billion reads. We characterized lincRNA transcriptome in the three brain regions and identified 20 differentially expressed lincRNAs (DELincRNAs) in BA11 for BD, 34 and 1 in BA24 and BA9 for SZ, respectively. Our results showed that these DELincRNAs exhibited brain region-specific patterns. Applying weighted gene co-expression network analysis, we revealed that DELincRNAs together with other genes can function as modules to perform different functions in different brain regions, such as immune system development in BA24 and oligodendrocyte differentiation in BA9. Additionally, we found that DNA methylation alteration could partly explain the dysregulation of lincRNAs, some of which could function as enhancers in the pathogenesis of major psychosis. Together, we performed systematical characterization of dysfunctional lincRNAs in multiple brain regions of major psychosis, which provided a valuable resource to understand their roles in SZ and BD pathology and helped to discover novel biomarkers.
Highlights
Schizophrenia (SZ) and bipolar disorder (BD), together termed “major psychosis”, both affect approximately 1% of the world’s population and lead to severe impact on the life quality of patients [1]
We identified three dysfunctional lincRNA modules based on weighted gene co-expression network analysis (WGCNA), revealing that DELincRNAs cooperating with important protein-coding genes participate in distinct biological processes in different brain regions
We performed RNA sequencing on three brain regions namely the BA11, BA24 and BA9 from SZ and BD patients and psychiatrically normal individuals
Summary
Schizophrenia (SZ) and bipolar disorder (BD), together termed “major psychosis”, both affect approximately 1% of the world’s population and lead to severe impact on the life quality of patients [1]. Previous studies of SZ and BD mostly focused on the genetic factors and identified several disease-associated risk genes or variations [2, 3]. High-throughput analysis of gene expression profiles provided additional insight into the potential biological processes implicated in SZ and BD [4]. The biological mechanisms underlying the pathophysiology of the disorders still need further investigation. RNA-seq-based transcriptome analyses uncovered a large number of long intergenic non-coding RNAs (lincRNAs) that are a class of important regulatory molecules in gene expression and various diseases [5, 6]. LincRNAs display prominently spatial and temporal expression and show highly specific expression in the www.impactjournals.com/oncotarget
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
