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Screening for the key mRNA SNP targets associated with pathogenesis of neonatal hypoxia-ischemic brain damage by RNA sequencing

Liu-Lin Xiong 1,3 , Lu-Lu Xue 2 , Mohammed Al-Hawwas 3 , Jin Huang 2 , Rui-Ze Niu 2 , Ya-Xin Tan 2 , Yang Xu 4 , Ying-Ying Su 4 , Jia Liu 2 , Ting-Hua Wang 2,4   

  1. 1 Department of Anesthesiology, Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, China
    2 Animal Zoology Department, Kunming Medical University, Kunming, Yunnan, China
    3 School of Pharmacy and Medical Sciences, Sansom Institute, University of South Australia, Adelaide, Australia
    4 Institute of Neurological Disease, Department of Anesthesiology, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
  • Online:2019-12-19
  • Contact: Jia Liu, liujiaaixuexi@126.com; Ting-Hua Wang, wangtinghua@vip.163.com
  • Supported by:

    This study was supported by Natural Science Fund of Yunnan Province (No. 2010ZC109), and National Natural Science Foundation of China (No. NSF 81601074) and was also supported by Sichuan provincial scientific grant (No. 2017SZ0145)

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Abstract:

Single-nucleotide polymorphisms (SNPs) were involved in certain diseases. However, the influences of SNPs on the pathogenesis of neonatal hypoxia-ischemic brain damage (HIBD) remain elusive. This study aimed to investigate the differential expression of mRNAs and the relatedness of SNPs with neonatal HIBD to identify potential etiological targets for HIBD. Seven-day postnatal rats were used to establish HIBD model, and the expression profiles of mRNA and SNP were analyzed in HI-brains using RNA sequencing and compared to control-brains. Genes exhibiting SNPs associated with HIBD were identified and studied by gene ontology (GO) and pathway analysis to identify their possible mechanism to initiate the disease. The results revealed 89 up-regulated genes exhibiting SNPs that mainly located on chromosome 1 and 2. Additionally, GO analysis indicated that the SNPs exhibiting up-regulated genes are mainly involved with angiogenesis, wound healing and glutamatergic synapse and biological processing of calcium-activated chloride channels. Signaling pathways analysis indicated that deferentially expressed genes play a role in glutamatergic synapse, longterm depression and oxytocin signaling pathway. Moreover, the intersection analysis of high throughput screening via Pubmed and gene sequencing for SNP showed that CSRNP1, DUSP5 and LRRC25 were most innovative and relative to HIE. They were verified to significantly up-regulate by qPCR in human neurons with OGD. Thus, the CSRNP1, DUSP5 and LRRC25 displaying SNPs may be accountable for the pathogenesis of HIBD, and are closely relevant to the development of HIBD. It is possible that our finding may be considered as a novel direction for further research on HIBD.

Key words: mRNA, single-nucleotide polymorphism, pathogenesis, neonatal hypoxia-ischemic brain damage, RNA sequencing