Full Text:   <622>

Summary:  <195>

Suppl. Mater.: 

CLC number: R49

On-line Access: 2018-04-04

Received: 2017-04-05

Revision Accepted: 2017-08-16

Crosschecked: 2018-03-08

Cited: 0

Clicked: 1447

Citations:  Bibtex RefMan EndNote GB/T7714

 ORCID:

Li-ning Su

https://orcid.org/0000-0001-8118-7601

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Journal of Zhejiang University SCIENCE B 2018 Vol.19 No.4 P.293-304

10.1631/jzus.B1700179


Network analysis of microRNAs, transcription factors, and target genes involved in axon regeneration


Author(s):  Li-ning Su, Xiao-qing Song, Zhan-xia Xue, Chen-qing Zheng, Hai-feng Yin, Hui-ping Wei

Affiliation(s):  Department of Basic Medicine, Hebei North University, Zhangjiakou 075029, China; more

Corresponding email(s):   whp123456@sina.com

Key Words:  Transcription factors, miRNAs, Target genes, Axon, Network analysis


Li-ning Su, Xiao-qing Song, Zhan-xia Xue, Chen-qing Zheng, Hai-feng Yin, Hui-ping Wei. Network analysis of microRNAs, transcription factors, and target genes involved in axon regeneration[J]. Journal of Zhejiang University Science B, 2018, 19(4): 293-304.

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author="Li-ning Su, Xiao-qing Song, Zhan-xia Xue, Chen-qing Zheng, Hai-feng Yin, Hui-ping Wei",
journal="Journal of Zhejiang University Science B",
volume="19",
number="4",
pages="293-304",
year="2018",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B1700179"
}

%0 Journal Article
%T Network analysis of microRNAs, transcription factors, and target genes involved in axon regeneration
%A Li-ning Su
%A Xiao-qing Song
%A Zhan-xia Xue
%A Chen-qing Zheng
%A Hai-feng Yin
%A Hui-ping Wei
%J Journal of Zhejiang University SCIENCE B
%V 19
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%P 293-304
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%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1700179

TY - JOUR
T1 - Network analysis of microRNAs, transcription factors, and target genes involved in axon regeneration
A1 - Li-ning Su
A1 - Xiao-qing Song
A1 - Zhan-xia Xue
A1 - Chen-qing Zheng
A1 - Hai-feng Yin
A1 - Hui-ping Wei
J0 - Journal of Zhejiang University Science B
VL - 19
IS - 4
SP - 293
EP - 304
%@ 1673-1581
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PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1700179


Abstract: 
axon regeneration is crucial for recovery from neurological diseases. Numerous studies have identified several genes, microRNAs (miRNAs), and transcription factors (TFs) that influence axon regeneration. However, the regulatory networks involved have not been fully elucidated. In the present study, we analyzed a regulatory network of 51 miRNAs, 27 TFs, and 59 target genes, which is involved in axon regeneration. We identified 359 pairs of feed-forward loops (FFLs), seven important genes (Nap1l1, Arhgef12, Sema6d, Akt3, Trim2, Rab11fip2, and Rps6ka3), six important miRNAs (hsa-miR-204-5p, hsa-miR-124-3p, hsa-miR-26a-5p, hsa-miR-16-5p, hsa-miR-17-5p, and hsa-miR-15b-5p), and eight important TFs (Smada2, Fli1, Wt1, Sp6, Sp3, Smad4, Smad5, and Creb1), which appear to play an important role in axon regeneration. Functional enrichment analysis revealed that axon-associated genes are involved mainly in the regulation of cellular component organization, axonogenesis, and cell morphogenesis during neuronal differentiation. However, these findings need to be validated by further studies.

神经轴突再生过程中微小RNA(miRNA)、转录因子和靶基因的网络功能分析

创新点:本研究比较详细地阐明了与神经轴突再生相关的微小RNA(miRNA)、转录因子和靶基因的相互作用关系,为神经系统疾病的恢复奠定基础.
方法:本研究从基因表达综合数据库中获得与轴突再生相关的转录因子和基因数据,利用文献报道及生物信息学数据库预测的方法筛选与轴突再生相关的基因靶向miRNA.利用生物信息学方法分析了三者之间的网络作用关系,预测了在相互作用网络中发挥重要作用的节点.最后对目标基因的基因本体(GO)功能进行了富集.
结论:通过分析,初步筛选了与神经轴突再生相关的51个miRNA、27个转录因子和59个靶标基因.进一步分析得到359对前馈环路,在此基础上推测了神经轴突再生过程中发挥重要作用的7个核心基因(Nap1l1Arhgef12Sema6dAkt3Trim2Rab11fip2Rps6ka3),6个miRNA(hsa-miR-204-5p、hsa-miR-124-3p、hsa-miR-26a-5p、hsa-miR-16-5p、hsa-miR-17-5p和hsa-miR-15b-5p)和8个转录因子(Smada2、Fli1、Wt1、Sp6、Sp3、 Smad4、Smad5和Creb1).

关键词:转录因子;miRNA;靶基因;神经轴突;网络分析

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

Reference

[1]Baldwin KT, Giger RJ, 2015. Insights into the physiological role of CNS regeneration inhibitors. Front Mol Neurosci, 8:23.

[2]Baronchelli S, La Spada A, Conforti P, et al., 2015. Investigating DNA methylation dynamics and safety of human embryonic stem cell differentiation towards striatal neurons. Stem Cells Dev, 24(20):2366-2377.

[3]Bigler RL, Kamande JW, Dumitru R, et al., 2016. Axonal mRNA in human embryonic stem cell derived neurons. BioRxiv, 066142.

[4]Boch J, Bonas U, 2010. Xanthomonas AvrBs3 family-type III effectors: discovery and function. Ann Rev Phytopathol, 48(1):419-436.

[5]Chesnutt C, Niswander L, 2004. Plasmid-based short-hairpin RNA interference in the chicken embryo. Genesis, 39(2): 73-78.

[6]Dahle O, Kuehn MR, 2016. Inhibiting Smad2/3 signaling in pluripotent mouse embryonic stem cells enhances endoderm formation by increasing transcriptional priming of lineage-specifying target genes. Dev Dyn, 245(7):807-815.

[7]Debanne D, Campanac E, Bialowas A, et al., 2011. Axon physiology. Physiol Rev, 91(2):555-602.

[8]Easton DM, 2005. Voltage-clamp predictions by gompertz kinetics model relating squid-axon Na+-gating and ionic currents. Int J Neurosci, 115(10):1415-1441.

[9]Evan G, Harrington E, Fanidi A, et al., 1994. Integrated control of cell proliferation and cell death by the c-myc oncogene. Philos Trans R Soc Lond B Biol Sci, 345(1313):269-275.

[10]Ferguson TA, Son YJ, 2011. Extrinsic and intrinsic determinants of nerve regeneration. J Tissue Eng, 2(1):1-12.

[11]Freitas AE, Machado DG, Budni J, et al., 2013. Fluoxetine modulates hippocampal cell signaling pathways implicated in neuroplasticity in olfactory bulbectomized mice. Behav Brain Res, 237:176-184.

[12]Geoffroy CG, Zheng B, 2014. Myelin-associated inhibitors in axonal growth after CNS injury. Curr Opin Neurobiol, 27:31-38.

[13]Hazen VM, Phana KD, Hudiburgha S, et al., 2011. Inhibitory Smads differentially regulate cell fate specification and axon dynamics in the dorsal spinal cord. Dev Biol, 2(356): 566-575.

[14]Hu W, He Y, Xiong Y, et al., 2016. Derivation, expansion, and motor neuron differentiation of human-induced pluripotent stem cells with non-integrating episomal vectors and a defined xenogeneic-free culture system. Mol Neurobiol, 53(3):1589-1600.

[15]Huang ZR, Hu ZZ, Xie P, et al., 2017. Tyrosine-mutated AAV2-mediated shRNA silencing of PTEN promotes axon regeneration of adult optic nerve. PLoS ONE, 12(3): e0174096.

[16]Irizarry RA, Hobbs B, Collin F, et al., 2003. Exploration, normalization, and summaries of high density oligonucleotide array probe level data. Biostatistics, 4(2):249-264.

[17]Jiang JJ, Liu CM, Zhang BY, et al., 2015. MicroRNA-26a supports mammalian axon regeneration in vivo by suppressing GSK3β expression. Cell Death Dis, 6:e1865.

[18]Kunik D, 2011. Laser-based single-axon transection for high-content axon injury and regeneration studies. PLoS ONE, 6(11):e26832.

[19]Lee TI, Young RA, 2000. Transcription of eukaryotic protein-coding genes. Ann Rev Genet, 34(1):77-137.

[20]Lin Y, Zhang Q, Zhang HM, et al., 2015. Transcription factor and miRNA co-regulatory network reveals shared and specific regulators in the development of B cell and T cell. Sci Rep, 5:15215.

[21]Lobe CG, 1992. Transcription factors and mammalian development. Curr Top Dev Biol, 27:351-383.

[22]McKerracher L, Rosen KM, 2015. MAG, myelin and overcoming growth inhibition in the CNS. Front Mol Neurosci, 8:51.

[23]Miao L, Yang L, Huang H, et al., 2016. mTORC1 is necessary but mTORC2 and GSK3β are inhibitory for AKT3-induced axon regeneration in the central nervous system. eLife, 5:e14908.

[24]Natera-Naranjo O, Aschrafi A, Gioio AE, et al., 2010. Identification and quantitative analyses of microRNAs located inhe distal axons of sympathetic neurons. RNA, 16(8): 1516-1529.

[25]Osborne CK, Schiff R, Fuqua SA, et al., 2001. Estrogen receptor: current understanding of its activation and modulation. Clin Cancer Res, 7(12 Suppl):4338s-4342s.

[26]Pullamsetti SS, Perros F, Chelladurai P, et al., 2016. Transcription factors, transcriptional coregulators, and epigenetic modulation in the control of pulmonary vascular cell phenotype: therapeutic implications for pulmonary hypertension. Pulm Circ, 6(4):448-464.

[27]Saijilafu, Hur EM, Jiao ZX, et al., 2013. PI3K-GSK3 signaling regulates mammalian axon regeneration by inducing the expression of Smad1. Nat Commun, 4:2690.

[28]Shannon P, Markiel A, Ozier O, et al., 2003. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res, 13(11):2498-2504.

[29]Stegmuller J, Huynh MA, Yuan Z, et al., 2008. TGFβ-Smad2 signaling regulates the Cdh1-APC/SnoN pathway of axonal morphogenesis. J Neurosci, 28(8):1961-1969.

[30]Su LN, Song XQ, Wei HP, et al., 2017a. Identification of neuron-related genes for cell therapy of neurological disorders by network analysis. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 18(2):172-182.

[31]Su LN, Wang YB, Wang CG, et al., 2017b. Network analysis identifies common genes associated with obesity in six obesity-related diseases. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 18(8):727-732.

[32]Tan Y, Zhang B, Wu T, et al., 2009. Transcriptional inhibiton of Hoxd4 expression by miRNA-10a in human breast cancer cells. BMC Mol Biol, 10:12.

[33]Torres L, Juarez U, Garcia L, et al., 2015. External ear microRNA expression profiles during mouse development. Int J Dev Biol, 59(10-12):497-503.

[34]Venkatesh I, Blackmore MG, 2017. Selecting optimal combinations of transcription factors to promote axon regeneration: why mechanisms matter. Neurosci Lett, 652(23): 64-73.

[35]Wang H, Xu Z, Ma M, et al., 2016. Network analysis of microRNAs, transcription factors, target genes and host genes in nasopharyngeal carcinoma. Oncol Lett, 11(6): 3821-3828.

[36]Yu P, Zhang YP, Shields LB, et al., 2011. Inhibitor of DNA binding 2 promotes sensory axonal growth after SCI. Exp Neurol, 231(1):38-44.

[37]List of electronic supplementary materials

[38]Table S1 Information of DEGs between Axon hESC-Neuron and Whole hESC-Neuron

[39]Table S2 Overlapping genes between DEGs and genes related to axon and genes in the same family with overlapping genes (Genes Cluster 1)

[40]Table S3 Mature miRNAs related to human axon

[41]Table S4 Target genes of miRNAs (Genes Cluster 2)

[42]Table S5 TFs interaction with 59 genes (TFs Cluster 2)

[43]Table S6 TFs interaction with 51 miRNAs (TFs Cluster 3)

[44]Table S7 Feed-forward loops in the network

[45]Table S8 Gene ontology enrichment analysis of biological process

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