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Peer-reviewedCC BY-NC-NDBMC neuroscience

Whole-transcriptome sequencing reveals Alzheimer's disease-associated ceRNA regulatory networks and downstream pathways.

  • KeFei Duan1
  • Fangfang Zhan2,3
  • Yaodan Zhang4
  • Xinghang Wang5
  • Gaoteng Lin6
  • Xiaoyi Zhao7
  • Dan Yu8
  • Shida Duan9
  • Yuan Ma10
10 affiliations
  1. 1Cerebrovascular Diseases Department, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100000, China.
  2. 2Department of Rehabilitation, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, 350000, China.
  3. 3Department of Rehabilitation, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian, 350212, China.
  4. 4Department of Geriatrics, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, 450000, China.
  5. 5The Great Bay Area Center for Brain Research, Southern Medical University, Guangzhou, 510515, China.
  6. 6Department of Urology, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, China.
  7. 7Department of Nephrology, Affiliated Hospital of Chifeng University, Chifeng, 024000, China.
  8. 8Department of Imaging, Affiliated Hospital of Chifeng University, Chifeng, 024000, China.
  9. 9School of Software, Henan University, Kaifeng, 475000, China.
  10. 10Department of Urology, Beijing Jishuitan Hospital, Capital Medical University, No. 31, Xinjiekou East Street, Xicheng District, Beijing, 100010, China. [email protected].
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Abstract

Objective

Alzheimer's disease (AD) molecular mechanisms remain unclear, and effective therapies are lacking. This study employed whole-transcriptome sequencing to investigate the expression profiles of circRNAs, lncRNAs, miRNAs, and mRNAs in the hippocampus of APP/PS1 transgenic mice, aiming to identify ceRNA regulatory networks and clarify their roles in AD pathogenesis.Methods

Differentially expressed RNAs were integrated into ceRNA networks, and programmed cell death-related pathways were analyzed using GO and KEGG. The computationally predicted circRNA_13083/miR-298-5p/CD14 axis was preliminarily evaluated in vitro using siRNA-mediated CD14 knockdown in microglial and neuronal AD models. Expression of CD14, NF-κB components, and NLRP3 markers was measured by qRT-PCR, while secreted IL-1β and IL-18 protein levels were quantified via ELISA. Neuronal survival was assessed via CCK-8 assays.Results

Transcriptome analysis revealed 376 differentially expressed mRNAs, 491 lncRNAs, 5,253 circRNAs, and 21 miRNAs, which formed extensive ceRNA interaction networks. Functional enrichment highlighted programmed cell death pathways, including NF-κB and inflammasome signaling. The circRNA_13083/miR-298-5p/CD14 axis emerged as a key regulatory node. qRT-PCR confirmed elevated CD14 expression in AD models. CD14 knockdown significantly attenuated Aβ1-42-induced NF-κB activation, NLRP3 inflammasome assembly, and proinflammatory cytokine release. Conditioned medium transfer experiments further demonstrated that CD14 silencing alleviated microglia-mediated neuronal damage and improved HT-22 cell survival.Conclusion

Whole-transcriptome sequencing uncovered extensive ceRNA regulatory networks in AD hippocampus, with the circRNA_13083/miR-298-5p/CD14 axis potentially implicated in neuroinflammation and programmed cell death through NF-κB signaling. Silencing CD14 mitigates microglial activation and neuronal injury, highlighting its potential as a therapeutic target for AD.

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Cite

BibTeXRIS
BibTeX
@article{duan2026wholetranscriptome,
  title = {{Whole-transcriptome sequencing reveals Alzheimer's disease-associated ceRNA regulatory networks and downstream pathways.}},
  author = {KeFei Duan and Fangfang Zhan and Yaodan Zhang and Xinghang Wang and Gaoteng Lin and Xiaoyi Zhao and Dan Yu and Shida Duan and Yuan Ma},
  journal = {BMC neuroscience},
  year = {2026},
  month = jul,
  doi = {10.1186/s12868-026-01030-5},
  url = {https://europepmc.org/article/MED/42907771},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - Whole-transcriptome sequencing reveals Alzheimer's disease-associated ceRNA regulatory networks and downstream pathways.
AU  - KeFei Duan
AU  - Fangfang Zhan
AU  - Yaodan Zhang
AU  - Xinghang Wang
AU  - Gaoteng Lin
AU  - Xiaoyi Zhao
AU  - Dan Yu
AU  - Shida Duan
AU  - Yuan Ma
PY  - 2026
DA  - 2026/07/01
JO  - BMC neuroscience
DO  - 10.1186/s12868-026-01030-5
UR  - https://europepmc.org/article/MED/42907771
AB  - Objective  Alzheimer's disease (AD) molecular mechanisms remain unclear, and effective therapies are lacking. This study employed whole-transcriptome sequencing to investigate the expression profiles of circRNAs, lncRNAs, miRNAs, and mRNAs in the hippocampus of APP/PS1 transgenic mice, aiming to identify ceRNA regulatory networks and clarify their roles in AD pathogenesis.Methods  Differentially expressed RNAs were integrated into ceRNA networks, and programmed cell death-related pathways were analyzed using GO and KEGG. The computationally predicted circRNA_13083/miR-298-5p/CD14 axis was preliminarily evaluated in vitro using siRNA-mediated CD14 knockdown in microglial and neuronal AD models. Expression of CD14, NF-κB components, and NLRP3 markers was measured by qRT-PCR, while secreted IL-1β and IL-18 protein levels were quantified via ELISA. Neuronal survival was assessed via CCK-8 assays.Results  Transcriptome analysis revealed 376 differentially expressed mRNAs, 491 lncRNAs, 5,253 circRNAs, and 21 miRNAs, which formed extensive ceRNA interaction networks. Functional enrichment highlighted programmed cell death pathways, including NF-κB and inflammasome signaling. The circRNA_13083/miR-298-5p/CD14 axis emerged as a key regulatory node. qRT-PCR confirmed elevated CD14 expression in AD models. CD14 knockdown significantly attenuated Aβ1-42-induced NF-κB activation, NLRP3 inflammasome assembly, and proinflammatory cytokine release. Conditioned medium transfer experiments further demonstrated that CD14 silencing alleviated microglia-mediated neuronal damage and improved HT-22 cell survival.Conclusion  Whole-transcriptome sequencing uncovered extensive ceRNA regulatory networks in AD hippocampus, with the circRNA_13083/miR-298-5p/CD14 axis potentially implicated in neuroinflammation and programmed cell death through NF-κB signaling. Silencing CD14 mitigates microglial activation and neuronal injury, highlighting its potential as a therapeutic target for AD.
SN  - 1471-2202
ER  -