Comprehensive analysis of circRNA expression profile and circRNA-miRNA-mRNA network susceptibility to very early-onset schizophrenia
Huanhuan Huang,
Jie Luo,
Yanjie Qi,
Yuanzhen Wu,
Junhui Qi,
Xiuping Yan,
Gaoyang Xu,
Fan He,
Yi Zheng
Affiliations
Huanhuan Huang
National Clinical Research Center for Mental Disorders, Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Beijing Institute for Brain Disorders Capital Medical University
Jie Luo
National Clinical Research Center for Mental Disorders, Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Beijing Institute for Brain Disorders Capital Medical University
Yanjie Qi
National Clinical Research Center for Mental Disorders, Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Beijing Institute for Brain Disorders Capital Medical University
Yuanzhen Wu
National Clinical Research Center for Mental Disorders, Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Beijing Institute for Brain Disorders Capital Medical University
Junhui Qi
National Clinical Research Center for Mental Disorders, Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Beijing Institute for Brain Disorders Capital Medical University
Xiuping Yan
National Clinical Research Center for Mental Disorders, Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Beijing Institute for Brain Disorders Capital Medical University
Gaoyang Xu
National Clinical Research Center for Mental Disorders, Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Beijing Institute for Brain Disorders Capital Medical University
Fan He
National Clinical Research Center for Mental Disorders, Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Beijing Institute for Brain Disorders Capital Medical University
Yi Zheng
National Clinical Research Center for Mental Disorders, Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Beijing Institute for Brain Disorders Capital Medical University
Abstract To explore the potential role of circular RNAs (circRNAs) in children developing very early-onset schizophrenia (VEOS). Total RNA was extracted from the plasma samples of 10 VEOS patients and eight healthy controls. Expression profiles of circRNAs, micro RNAs (miRNAs), and messenger RNAs (mRNAs) were analyzed using RNA-seq. The interaction networks between miRNAs and targets were predicted using the miRanda tool. A differentially expressed circRNA-miRNA-mRNA (ceRNA) network was further constructed. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of the target mRNAs in the ceRNA network were performed to predict the potential functions of their host genes. The patient group and the control group were also compared on the regulatory patterns of circRNAs on mRNAs. 1934 circRNAs were identified from the samples and reported for the first time in schizophrenia. The circRNA expression levels were lower in the VEOS group than in the healthy control group, and 1889 circRNAs were expressed only in the control group. Differential expression analysis (i.e., log2fold change > 1.5, p 0.05) identified 235 circRNAs (1 up-regulated, 234 down-regulated), 11 miRNAs (7 up-regulated, 4 down-regulated), and 2,308 mRNAs (1906 up-regulated, 402 down-regulated) respectively. In VEOS, a ceRNA network with 10 down-regulated circRNA targets, 6 up-regulated miRNAs, and 47 down-regulated mRNAs was constructed. The target genes were involved in the membrane, the signal transduction, and the cytoskeleton and transport pathways. Finally, different expression correlation patterns of circRNA and mRNA in the network were observed between the patient group and the control group. The current research is the first to reveal the differentially expressed circRNAs in the plasma of VEOS patients. A circRNA-miRNA-mRNA network was also conducted in this study. It may be implied that the circRNAs in this network are potential diagnostic biomarkers for VEOS and they play an important role in the onset and development of VEOS symptoms.
