Dataset Information

Integrated aqueous humor ceRNA and miRNA-TF-mRNA network analysis reveals potential molecular mechanisms governing primary open-angle glaucoma pathogenesis.

ABSTRACT:

Purpose

To conduct an integrated bioinformatics analysis of extant aqueous humor (AH) gene expression datasets in order to identify key genes and the regulatory mechanism governing primary open-angle glaucoma (POAG) progression.

Methods

Two datasets (GSE101727 and GSE105269) were downloaded from the Gene Expression Omnibus, and the messenger RNAs (mRNAs), microRNAs (miRNAs), and long noncoding RNAs (lncRNAs) were identified between controls and POAG patients. Differentially expressed (DE) mRNAs and DElncRNAs were then subjected to pathway enrichment analyses, after which a protein-protein interaction (PPI) network was generated. This network was then expanded to establish lncRNA-miRNA-mRNA and miRNA-transcription factor (TF)-mRNA networks.

Results

The GSE101727 dataset was used to identify 2746 DElncRNAs and 2208 DEmRNAs, while the GSE105269 dataset was used to identify 45 DEmiRNAs. We ultimately constructed a competing endogenous RNA (ceRNA) network incorporating 47 lncRNAs, six miRNAs, and 17 mRNAs. The proteins encoded by these 17 hub mRNAs were found to be significantly enriched for activities that may be linked to POAG pathogenesis. In addition, we generated a miRNA-TF-mRNA regulatory network containing two miRNAs (miR-135a-5p and miR-139-5p), five TFs (TGIF2, TCF3, FOS, and so on), and five mRNAs (SHISA7, ST6GAL2, TXNIP, and so on).

Conclusion

The SHISA7, ST6GAL2, TXNIP, FOS, and DCBLD2 genes may be viable therapeutic targets for the prevention or treatment of POAG and are regulated by the TFs (TGIF2, HNF1A, TCF3, and FOS).

SUBMITTER: Wang X

PROVIDER: S-EPMC10228979 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Publications

Integrated aqueous humor ceRNA and miRNA-TF-mRNA network analysis reveals potential molecular mechanisms governing primary open-angle glaucoma pathogenesis.

Wang Xiaoqin X Chen Ming M Liu Longqian L Zeng Liuzhi L

Indian journal of ophthalmology 20230201 2

<h4>Purpose</h4>To conduct an integrated bioinformatics analysis of extant aqueous humor (AH) gene expression datasets in order to identify key genes and the regulatory mechanism governing primary open-angle glaucoma (POAG) progression.<h4>Methods</h4>Two datasets (GSE101727 and GSE105269) were downloaded from the Gene Expression Omnibus, and the messenger RNAs (mRNAs), microRNAs (miRNAs), and long noncoding RNAs (lncRNAs) were identified between controls and POAG patients. Differentially expres ...[more]

PMID: 36727359

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Project description:BackgroundEndothelin is a potent vasoconstrictor and contributes to the regulation of vascular perfusion. Aberrant endothelin-1 (ET-1) levels in aqueous humor have been reported across a variety of vascular diseases of the eye, including glaucoma. These findings suggest that dysregulation of ET-1 production may contribute to glaucoma pathophysiology. In this study, aqueous humor from patients undergoing ocular surgery was assayed for ET-1 abundance and related to the presence of glaucoma.PatientsOpen angle glaucoma patients (n=62 total) from the ophthalmology clinics of the University of Iowa Hospitals and Clinics were enrolled in this study and organized into three distinct cohorts based on their diagnostic criteria, including those with primary open angle glaucoma (POAG, n=25 patients), normal tension glaucoma (NTG, n=17 patients), exfoliation glaucoma (XFG, n=8 patients), and normal controls (n=12 patients).MethodsAqueous humor was collected intraoperatively from patients undergoing surgeries for glaucoma (including minimally invasive glaucoma surgeries, trabeculectomy, or glaucoma drainage device implantation) for samples in the glaucoma cohorts and cataract extraction for those in the control cohort. Aqueous humor was assayed by ELISA to measure and compare ET-1 abundance between the glaucoma cohorts and control cohort. ET-1 levels were also analyzed with linear regression to control for the covariates of age and sex.ResultsET-1 was significantly elevated in the aqueous humor of patients in the POAG (mean ± SD: 7.8 ± 5.1 pg/mL; p = 0.002) and NTG cohorts (6.1 ± 3.0 pg/mL; p = 0.030) compared to the control (4.0 ± 1.9 pg/mL). No significant difference in aqueous ET-1 was detected in the XFG cohort (6.2 ± 4.5 pg/mL; p = 0.230) compared to the control. Significantly higher ET-1 levels were detected in a merged grouping of all glaucoma cohorts (POAG, NTG, XFG) relative to controls (p = 0.021). Analysis of covariance indicated neither age nor sex was associated with ET-1 level (p = 0.60 and p = 0.27), respectively. Controlling for age and sex had minimal influence on the comparison of ET-1 levels in the POAG versus control cohort (p = 0.018) and nominal influence on the comparisons between the NTG (p = 0.089) or XFG cohort (p = 0.15) relative to the control.ConclusionsElevated ET-1 in aqueous humor was associated with POAG and NTG compared to controls amongst cohorts of patients at the University of Iowa. These data suggest that dysregulation of vascular perfusion may have a role in the pathophysiology of POAG. The analyses of NTG and XFG samples were limited by the relatively small sample sizes.

Dataset Information

Integrated aqueous humor ceRNA and miRNA-TF-mRNA network analysis reveals potential molecular mechanisms governing primary open-angle glaucoma pathogenesis.

Purpose

Methods

Results

Conclusion

Publications

Integrated aqueous humor ceRNA and miRNA-TF-mRNA network analysis reveals potential molecular mechanisms governing primary open-angle glaucoma pathogenesis.

Similar Datasets

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