Neural Regeneration Research ›› 2021, Vol. 16 ›› Issue (10): 2099-2108.doi: 10.4103/1673-5374.308104

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MicroRNA and mRNA profiling of cerebral cortex in a transgenic mouse model of Alzheimer’s disease by RNA sequencing

Li Zeng1, #, Hai-Lun Jiang1, #, Ghulam Md Ashraf2, 3, Zhuo-Rong Li1, *, Rui Liu1, *   

  1. 1Organic Chemistry and Function Laboratory, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; 2King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia; 3Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
  • Online:2021-10-15 Published:2021-03-19
  • Contact: Rui Liu, PhD, liurui@imb.pumc.edu.cn; Zhuo-Rong Li, MD, lizhourong@imb.pumc.edu.cn.
  • Supported by:
    This study was supported by the National Natural Science Foundation of China (General Program), No. 81673411; the United Fund Project of National Natural Science Foundation of China, No. U1803281; Young Medical Talents Award Project of Chinese Academy of Medical Sciences, No. 2018RC350013; and Chinese Academy of Medical Sciences Innovation Project for Medical Science, No. 2017-I2M-1-016 (all to RL).

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Abstract: In a previous study, we found that long non-coding genes in Alzheimer’s disease (AD) are a result of endogenous gene disorders caused by the recruitment of microRNA (miRNA) and mRNA, and that miR-200a-3p and other representative miRNAs can mediate cognitive impairment and thus serve as new biomarkers for AD. In this study, we investigated the abnormal expression of miRNA and mRNA and the pathogenesis of AD at the epigenetic level. To this aim, we performed RNA sequencing and an integrative analysis of the cerebral cortex of the widely used amyloid precursor protein and presenilin-1 double transgenic mouse model of AD. Overall, 129 mRNAs and 68 miRNAs were aberrantly expressed. Among these, eight down-regulated miRNAs and seven up-regulated miRNAs appeared as promising noninvasive biomarkers and therapeutic targets. The main enriched signaling pathways involved mitogen-activated kinase protein, phosphatidylinositol 3-kinase-protein kinase B, mechanistic target of rapamycin kinase, forkhead box O, and autophagy. An miRNA-mRNA network between dysregulated miRNAs and corresponding target genes connected with AD progression was also constructed. These miRNAs and mRNAs are potential biomarkers and therapeutic targets for new treatment strategies, early diagnosis, and prevention of AD. The present results provide a novel perspective on the role of miRNAs and mRNAs in AD. This study was approved by the Experimental Animal Care and Use Committee of Institute of Medicinal Biotechnology of Beijing, China (approval No. IMB-201909-D6) on September 6, 2019.

Key words: 3?-untranslated region, Alzheimer’s disease, biomarker, cerebral cortex, Gene Ontology, high-throughput sequencing, intracellular neurofibrillary tangles, microtubule-associated protein-τ, miRNA-mRNA network, presenilin 1

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