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Research Paper|Volume 11, Issue 23|pp 11673—11685

Identification of molecular correlations of RBM8A with autophagy in Alzheimer's disease

Donghua Zou1, Rongjie Li1, Xiaohua Huang2, Guoying Chen1, Ying Liu1, Youshi Meng1, Yimei Wang1, Yuan Wu3, Yingwei Mao4
  • 1Department of Neurology, The Fifth Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530022, China
  • 2Department of Neurology, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise 533000, China
  • 3Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, China
  • 4Department of Biology, Pennsylvania State University, University Park, PA 16802, USA
* Equal contribution
Received: October 12, 2019Accepted: November 23, 2019Published: December 9, 2019
https://doi.org/10.18632/aging.102571

Copyright © 2019 Zou 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

Our previous studies revealed RBM8A may play a role in various progressive neurological diseases. The present study aimed to explore the role of RBM8A in Alzheimer's disease (AD). RBM8A is significantly down-regulated in AD. Interestingly, 9186 differentially expressed genes are overlapped from comparisons of AD versus control and RBM8A-low versus RBM8A-high. Weight gene correlation analysis was performed and 9 functional modules were identified. Modules positively correlated with AD and RBM8A-low are significantly involved in the RAP1 signaling pathway, PI3K−AKT signaling pathway, hematopoietic cell lineage, autophagy and APELIN signaling pathway. Fifteen genes (RBM8A, RHBDF2, TNFRSF10B, ACP1, ANKRD39, CA10, CAMK4, CBLN4, LOC284214, NOVA1, PAK1, PPEF1, RGS4, TCEB1 and TMEM118) are identified as hub genes, and the hub gene-based LASSO model can accurately predict the occurrence of AD (AUC = 0.948). Moreover, the RBM8A-module-pathway network was constructed, and low expression of RBM8A down-regulates multiple module genes, including FIP200, Beclin 1, NRBF2, VPS15 and ATG12, which composes key complexes of autophagy. Thus, our study supports that low expression of RBM8A correlates with the decrease of the components of key complexes in autophagy, which could potentially contribute to pathophysiological changes of AD.