Identification of a chromatin regulator signature and potential candidate drugs for primary open-angle glaucoma.

Xinyue Zhang, Lulu Xiao, Xiaoyu Zhou, Jiahao Xu, Li Liao, Ping Wu, Zhimin Liao, Xuanchu Duan
Author Information
  1. Xinyue Zhang: Glaucoma Institute, Hunan Engineering Research Center for Glaucoma with Artificial Intelligence in Diagnosis and Application of New Materials, Changsha Aier Eye Hospital, Changsha, Hunan, China.
  2. Lulu Xiao: Glaucoma Institute, Hunan Engineering Research Center for Glaucoma with Artificial Intelligence in Diagnosis and Application of New Materials, Changsha Aier Eye Hospital, Changsha, Hunan, China.
  3. Xiaoyu Zhou: Glaucoma Institute, Hunan Engineering Research Center for Glaucoma with Artificial Intelligence in Diagnosis and Application of New Materials, Changsha Aier Eye Hospital, Changsha, Hunan, China.
  4. Jiahao Xu: Glaucoma Institute, Hunan Engineering Research Center for Glaucoma with Artificial Intelligence in Diagnosis and Application of New Materials, Changsha Aier Eye Hospital, Changsha, Hunan, China.
  5. Li Liao: Aier School of Ophthalmology, Central South University, Changsha, Hunan, China.
  6. Ping Wu: Aier School of Ophthalmology, Central South University, Changsha, Hunan, China.
  7. Zhimin Liao: Glaucoma Institute, Hunan Engineering Research Center for Glaucoma with Artificial Intelligence in Diagnosis and Application of New Materials, Changsha Aier Eye Hospital, Changsha, Hunan, China.
  8. Xuanchu Duan: Glaucoma Institute, Hunan Engineering Research Center for Glaucoma with Artificial Intelligence in Diagnosis and Application of New Materials, Changsha Aier Eye Hospital, Changsha, Hunan, China. ORCID

Abstract

AIMS: This research aims to establish a chromatin regulator (CR) signature to provide new epigenetic insights into the pathogenesis of primary open-angle glaucoma (POAG).
MATERIALS & METHODS: The expression profile of CRs in trabecular meshwork (TM) tissues was analyzed by bioinformatics analysis; The selected hub CRs were further verified by cell experiments.
RESULTS: We found the immune microenvironment of the TMwas changed in POAG patients and identified 3 differentially expressed CRs that were relevant to immunity. Then, we successfully constructed and proved a predicted signature based on these 3 CRs, which could effectively predict the risk of POAG. The genes co-expressed with these 3 CRs and miRNAs with are gulatory relationship were identified, and a miRNA-hub CR network was successfully constructed. The results of the Gene Set Enrichment analysis indicated that these 3 hub CRs were all associated with neurodegenerative diseases. Moreover, the human trabecular meshwork cell (HTMC) oxidative stress model was constructed, and KDM5B was significantly down-regulated in this cell model. Finally, we found 10 agents that might be helpful for patients with POAG.
CONCLUSIONS: Dysregulation of CR expression in TM tissues may be involved in the occurrence and progression of POAG through multiple mechanisms.

Keywords

References

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MeSH Term

Humans
Glaucoma, Open-Angle
Chromatin
Trabecular Meshwork
MicroRNAs
Epigenesis, Genetic
Gene Regulatory Networks
Oxidative Stress
Computational Biology
Jumonji Domain-Containing Histone Demethylases
Gene Expression Regulation

Chemicals

Chromatin
MicroRNAs
Jumonji Domain-Containing Histone Demethylases

Word Cloud

Created with Highcharts 10.0.0POAGCRschromatinCRsignaturetrabecularmeshworkcell3constructedregulatorprimaryopen-angleglaucomaexpressionTMtissuesanalysisfoundpatientsidentifiedsuccessfullyoxidativestressmodelAIMS:researchaimsestablishprovidenewepigeneticinsightspathogenesisMATERIALS&METHODS:profileanalyzedbioinformaticsselectedhubverifiedexperimentsRESULTS:immunemicroenvironmentTMwaschangeddifferentiallyexpressedrelevantimmunityprovedpredictedbasedeffectivelypredictriskgenesco-expressedmiRNAsgulatoryrelationshipmiRNA-hubnetworkresultsGeneSetEnrichmentindicated3 hubassociatedneurodegenerativediseasesMoreoverhumanHTMCKDM5Bsignificantlydown-regulatedFinally10agentsmighthelpfulCONCLUSIONS:DysregulationmayinvolvedoccurrenceprogressionmultiplemechanismsIdentificationpotentialcandidatedrugsGlaucomaregulators

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