Oncotarget

Research Papers: Pathology:

Systematically characterizing dysfunctional long intergenic non-coding RNAs in multiple brain regions of major psychosis

Jing Hu, Jinyuan Xu, Lin Pang, Hongying Zhao, Feng Li, Yulan Deng, Ling Liu, Yujia Lan, Xinxin Zhang, Tingting Zhao, Chaohan Xu, Chun Xu, Yun Xiao and Xia Li _

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Oncotarget. 2016; 7:71087-71098. https://doi.org/10.18632/oncotarget.12122

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Abstract

Jing Hu1,*, Jinyuan Xu1,*, Lin Pang1,*, Hongying Zhao1, Feng Li1, Yulan Deng1, Ling Liu1, Yujia Lan1, Xinxin Zhang1, Tingting Zhao2, Chaohan Xu1, Chun Xu3, Yun Xiao1 and Xia Li1

1 College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang, China

2 Department of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China

3 Department of Psychiatry, Texas Tech University Health Science Center, El Paso, Texas, United States of America

* These authors have contributed equally to this work

Correspondence to:

Xia Li, email:

Yun Xiao, email:

Chun Xu, email:

Keywords: long intergenic non-coding RNA, schizophrenia, bipolar disorder, brain region, RNA sequencing, Pathology Section

Received: March 08, 2016 Accepted: September 12, 2016 Published: September 19, 2016

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.


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