Investigation of Gene Regulatory Networks Associated with Autism Spectrum Disorder Based on MiRNA Expression in China

Fengzhen Huang; Zhe Long; Zhao Chen; Jiada Li; Zhengmao Hu; Rong Qiu; Wei Zhuang; Beisha Tang; Kun Xia; Hong Jiang

doi:10.1371/journal.pone.0129052

Investigation of Gene Regulatory Networks Associated with Autism Spectrum Disorder Based on MiRNA Expression in China

PLoS One. 2015 Jun 10;10(6):e0129052. doi: 10.1371/journal.pone.0129052. eCollection 2015.

Authors

Fengzhen Huang¹, Zhe Long², Zhao Chen², Jiada Li³, Zhengmao Hu³, Rong Qiu⁴, Wei Zhuang⁵, Beisha Tang⁶, Kun Xia³, Hong Jiang⁶

Affiliations

¹ Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, P. R. China; Department of Neurology at University of South China, The First People's Hospital of Chenzhou, Chenzhou, Hunan, 423000, P. R. China; Institute of Translational Medicine at University of South China, The First People's Hospital of Chenzhou, Chenzhou, Hunan, 423000, P. R. China.
² Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, P. R. China.
³ State Key Laboratory of Medical Genetics of China, Central South University, Changsha, Hunan,410078, P. R. China.
⁴ School of Information Science and Engineering, Central South University, Hunan, 410083, P. R. China; Hunan Engineering Laboratory for Advanced Control and Intelligent Automation, Hunan, 410083, P. R. China.
⁵ Department of Thoracic surgery, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, P. R. China.
⁶ Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, P. R. China; State Key Laboratory of Medical Genetics of China, Central South University, Changsha, Hunan,410078, P. R. China; Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, Hunan, 410008, P. R. China.

Abstract

Autism spectrum disorder (ASD) comprise a group of neurodevelopmental disorders characterized by deficits in social and communication capacities and repetitive behaviors. Increasing neuroscientific evidence indicates that the neuropathology of ASD is widespread and involves epigenetic regulation in the brain. Differentially expressed miRNAs in the peripheral blood from autism patients were identified by high-throughput miRNA microarray analyses. Five of these miRNAs were confirmed through quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis. A search for candidate target genes of the five confirmed miRNAs was performed through a Kyoto encyclopedia of genes and genomes (KEGG) biological pathways and Gene Ontology enrichment analysis of gene function to identify gene regulatory networks. To the best of our knowledge, this study provides the first global miRNA expression profile of ASD in China. The differentially expressed miR-34b may potentially explain the higher percentage of male ASD patients, and the aberrantly expressed miR-103a-3p may contribute to the abnormal ubiquitin-mediated proteolysis observed in ASD.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Asian People / genetics
Autism Spectrum Disorder / blood
Autism Spectrum Disorder / genetics*
Child
Child, Preschool
China
Epigenesis, Genetic
Female
Gene Expression Profiling / methods*
Gene Regulatory Networks*
Genetic Association Studies
Humans
Male
MicroRNAs / blood*
MicroRNAs / genetics
Oligonucleotide Array Sequence Analysis / methods*
Ubiquitin / metabolism

Substances

MIRN103 microRNA, human
MIRN34 microRNA, human
MicroRNAs
Ubiquitin

Grants and funding

This study was supported by the National Basic Research Program (973 Program) (Nos. 2012CB944601, 2012CB517902 and 2011CB510002 to Hong Jiang), the National Natural Science Foundation of China (Nos. 81410308019, 81471156, 81271260, 30971585 to Hong Jiang; No 31401135 to Rong Qiu), Hunan Funds for Distinguished Young Scientists (No. 14JJ1008 to Hong Jiang), Xinjiang Natural Science Foundation (No. 201318101-4 to Hong Jiang), Natural Science Foundation of Hunan Province (No 2012SK3194 to Wei Zhuang), the Undergraduate Innovation Project of Central South University (No. YB13028, 201410533324 to Hong Jiang), Graduate Innovation Project of Central South University (No. 2014zzts078 to Zhao Chen), Research projects of the First People's Hospital of Chenzhou (No. N2014-017, to Fengzhen Huang) and High-level medical personnel of Hunan province “225” Project. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.