Research Paper Volume 13, Issue 3 pp 4674—4695

Integrated analysis of microRNA and mRNA expression profiling identifies BAIAP3 as a novel target of dysregulated hsa-miR-1972 in age-related white matter lesions

Wen-Qing Huang1,2, *, , Qing Lin3,4,5,6, *, , Shuai Chen7,8, *, , Lixiang Sun2, *, , Qingjie Chen9, , Kehui Yi3,10, , Zhi Li2, , Qilin Ma3,4,5,6, &, , Chi-Meng Tzeng2,11, ,

  • 1 Shanghai Institute of Precision Medicine (SHIPM), Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
  • 2 Translational Medicine Research Center (TMRC), School of Pharmaceutical Sciences, Xiamen University, Xiamen, Fujian, China
  • 3 Department of Neurology, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China
  • 4 Xiamen Key Laboratory of Brain Center, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China
  • 5 School of Medicine, Xiamen University, Xiamen, Fujian, China
  • 6 The First Clinical College of Fujian Medical University, Fuzhou, Fujian, China
  • 7 Department of Otolaryngology-Head and Neck Surgery, Xiamen Key Laboratory of Otolaryngology-Head and Neck Surgery, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China
  • 8 Chen Zhi-nan Academician Workstation, Institute of Basic and Translational Medicine, Xi’an Medical University, Xi’an, Shanxi, China
  • 9 Department of Nuclear Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
  • 10 Department of Neurology, Zhongshan Xiamen Hospital, Fudan University, Xiamen, Fujian, China
  • 11 College of Pharmaceutical Sciences, Nanjing Tech University, Nanjing, Jiangsu, China
* Equal contribution

Received: August 12, 2020       Accepted: November 18, 2020       Published: February 9, 2021      

https://doi.org/10.18632/aging.202562
How to Cite

Copyright: © 2021 Huang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

White matter lesions known as leukoaraiosis (LA) are cerebral white matter hyperintensities observed in elderly individuals. Currently, no reliable molecular biomarkers are available for monitoring their progression over time. To identify biomarkers for the onset and progression of LA, we analyzed whole blood-based, microRNA expression profiles of leukoaraiosis, validated those exhibiting significant microRNA changes in clinical subjects by means of quantitative real-time polymerase chain reactions and determined the function of miRNA in cell lines by means of microRNA mimic transfection assays. A total of seven microRNAs were found to be significantly down-regulated in leukoaraiosis. Among the microRNAs, hsa-miR-1972 was downregulated during the early onset phase of leukoaraiosis, as confirmed in independent patients, and it was found to target leukoaraiosis-dependent BAIAP3, decreasing its expression in 293T cell lines. Functional enrichment analysis revealed that significantly dysregulated miRNAs-mRNAs changes associated with the onset of leukoaraiosis were involved in neurogenesis, neuronal development, and differentiation. Taken together, the study identified a set of candidate microRNA biomarkers that may usefully monitor the onset and progression of leukoaraiosis. Given the enrichment of leukoaraiosis-associated microRNAs and mRNAs in neuron part and membrane system, BAIAP3 could potentially represent a novel target of hsa-miR-1972 in leukoaraiosis through which microRNAs are involved in the pathogenesis of white matter lesions.

Abbreviations

BBB: blood-brain barrier; BDNF: brain-derived neurotrophic factor; CNS: central nervous system; DCV: dense-core vesicle exocytosis; LA: leukoaraiosis; miRNA: microRNA; MRI: magnetic resonance imaging; MUT: mutant-type; NC: negative control; SNPs: single nucleotide polymorphisms; WMH: white matter hyperintensities; WML: white matter lesions; WT: wild-type.