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Updated: Oct 9, 2025
Author Spotlight: Advancing Alzheimer's Research – Exploring Early Detection and Multi-Omics Approaches
Published on: December 15, 2023
Putative Factors Interfering Cell Cycle Re-Entry in Alzheimer's Disease: An Omics Study with Differential Expression
Sze Chung Yuen1, Simon Ming-Yuen Lee1, Siu-Wai Leung2,3
1State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China.
Background:
Neuronal cell cycle re-entry (CCR) is a mechanism, along with amyloid-β (Aβ) oligomers and hyperphosphorylated tau proteins, contributing to toxicity in Alzheimer's disease (AD).
Objective:
This study aimed to examine the putative factors in CCR based on evidence corroboration by combining meta-analysis and co-expression analysis of omic data.
Methods:
The differentially expressed genes (DEGs) and CCR-related modules were obtained through the differential analysis and co-expression of transcriptomic data, respectively. Differentially expressed microRNAs (DEmiRNAs) were extracted from the differential miRNA expression studies. The dysregulations of DEGs and DEmiRNAs as binary outcomes were independently analyzed by meta-analysis based on a random-effects model. The CCR-related modules were mapped to human protein-protein interaction databases to construct a network. The importance score of each node within the network was determined by the PageRank algorithm, and nodes that fit the pre-defined criteria were treated as putative CCR-related factors.
Results:
The meta-analysis identified 18,261 DEGs and 36 DEmiRNAs, including genes in the ubiquitination proteasome system, mitochondrial homeostasis, and CCR, and miRNAs associated with AD pathologies. The co-expression analysis identified 156 CCR-related modules to construct a protein-protein interaction network. Five genes, UBC, ESR1, EGFR, CUL3, and KRAS, were selected as putative CCR-related factors. Their functions suggested that the combined effects of cellular dyshomeostasis and receptors mediating Aβ toxicity from impaired ubiquitination proteasome system are involved in CCR.
Conclusion:
This study identified five genes as putative factors and revealed the significance of cellular dyshomeostasis in the CCR of AD.
Insights
Neuronal cell cycle re-entry (CCR) contributes to Alzheimer's disease (AD) toxicity. This study identified five key genes, highlighting cellular dyshomeostasis as a significant factor in AD-related CCR.
Area of Science:
- Neuroscience
- Genetics
- Bioinformatics
Background:
- Neuronal cell cycle re-entry (CCR) is implicated in Alzheimer's disease (AD) pathogenesis, alongside amyloid-β (Aβ) oligomers and hyperphosphorylated tau.
- Understanding the molecular drivers of CCR is crucial for developing effective AD therapies.
Purpose of the Study:
- To identify putative factors driving neuronal cell cycle re-entry (CCR) in Alzheimer's disease (AD).
- To corroborate evidence by integrating meta-analysis and co-expression analysis of omic data.
Main Methods:
- Performed meta-analysis on differentially expressed genes (DEGs) and microRNAs (DEmiRNAs) from transcriptomic and miRNA expression studies.
- Conducted co-expression analysis to identify CCR-related modules and constructed a protein-protein interaction network.
- Utilized the PageRank algorithm to identify key nodes (putative CCR-related factors) within the network.
Main Results:
- Identified 18,261 DEGs and 36 DEmiRNAs, implicating the ubiquitination proteasome system and mitochondrial homeostasis in CCR and AD.
- Constructed a protein-protein interaction network from 156 CCR-related modules.
- Selected five genes (UBC, ESR1, EGFR, CUL3, KRAS) as putative CCR factors, suggesting roles for cellular dyshomeostasis and Aβ toxicity mediation.
Conclusions:
- Identified five key genes as putative factors involved in neuronal cell cycle re-entry (CCR) in Alzheimer's disease (AD).
- Highlighted the critical role of cellular dyshomeostasis in mediating CCR within the context of AD.
