Relationship between the Pathogenesis of Glaucoma and miRNA

Guo, Ruru; Shen, Wencui; Su, Chang; Jiang, Shiwei; Wang, Jiantao

doi:10.1159/000450957

Cited by 41 publications

(29 citation statements)

References 54 publications

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“…miRNAs can regulate a variety of biological activities, including embryonic development, angiogenesis, cell differentiation, proliferation and apoptosis (8–10). With the development of next-generation sequencing and bioinformatics methods, differentially expressed miRNAs that are potentially involved in the pathogenesis of diseases, including cancers (11,12) and glaucoma (13–15), have been successfully identified. The targets of these miRNAs, as well as related signaling pathways, have also been predicted.…”

Section: Introductionmentioning

confidence: 99%

miR‑17‑5p regulates the proliferation and apoptosis of human trabecular meshwork cells by targeting phosphatase and tensin homolog

Wang

Bai

et al. 2019

Mol Med Report

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Glaucoma is one of the leading causes of blindness. Previous studies have indicated that the oxidative stress-induced apoptosis of trabecular meshwork cells (TMCs) may serve a key role in the pathogenesis of glaucoma, and that micro RNA(miR)-17-5p may be involved in this process. However, the specific mechanisms require further investigation. The aim of the present study was to investigate the effects of miR-17-5p on the proliferation and apoptosis of human TMCs (HTMCs) in response to oxidative stress. It was observed that exposure to H2O2 induced a significant decrease in the proliferation and a marked increase in the apoptosis of HTMCs. H2O2 exposure also suppressed the expression of miR-17-5p and promoted the expression of phosphatase and tensin homolog (PTEN). Furthermore, transient overexpression of miR-17-5p induced a significant increase in the proliferation and a significant decrease in the apoptosis of HTMCs by affecting the expression of PTEN, and the apoptosis-related proteins B-cell lymphoma-associated X protein (Bax), B-cell lymphoma-extra large (Bcl-xL) and B-cell lymphoma-2 (Bcl-2). However, knockdown of miR-17-5p demonstrated the opposite results. The results of a dual luciferase reporter assay demonstrated that PTEN may be a direct target of miR-17-5p. In conclusion, miR-17-5p was downregulated in HTMCs under oxidative conditions, and miR-17-5p may regulate the apoptosis of HTMCs by targeting PTEN. These results provide a novel theoretical basis and potential therapeutic target for the treatment of glaucoma.

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Section: Introductionmentioning

confidence: 99%

miR‑17‑5p regulates the proliferation and apoptosis of human trabecular meshwork cells by targeting phosphatase and tensin homolog

Wang

Bai

et al. 2019

Mol Med Report

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“…In eukaryotes, both TFs and miRNAs serve as primary regulators of gene expression, with TFs serving to directly control DNA transcription [13,14] and miRNAs functioning by binding to conserved MREs to disrupt target mRNA translation at the post-transcriptional level [15,16,17,18]. In prior analyses, miRNAs have been shown to control anterior chamber shape, IOP, and RGC apoptosis via the regulation of specific target genes [19]. In addition, there is evidence that miRNAs can regulate diverse biochemical pathways in the context of glaucoma [20], and miRNAs including miR-125b-5p have been detected at elevated levels in human AH relative to human serum [21,22].…”

Section: Discussionmentioning

confidence: 99%

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

Wang

Zeng²,

chen³

et al. 2020

Preprint

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Primary open-angle glaucoma (POAG) is the leading cause of blindness globally, which develops through complex and poorly understood biological mechanisms. Herein, we conducted an integrated bioinformatics analysis of extant aqueous humor (AH) gene expression datasets in order to identify key genes and regulatory mechanisms governing POAG progression. We downloaded AH gene expression datasets (GSE101727 and GSE105269) corresponding to healthy controls and POAG patients from the Gene Expression Omnibus. We then identified mRNAs, microRNAs (miRNAs), and long non-coding RNAs (lncRNAs) that were differentially expressed (DE) between control and POAG patients. DEmRNAs 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. In total, 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 37, 5, and 14 of these lncRNAs, miRNAs and mRNAs, respectively. The proteins encoded by these 14 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 2 miRNAs (miR-135a-5p and miR-139-5p), 5 TFs (TGIF2, TBX5, HNF1A, TCF3, and FOS) and 5 mRNAs (SHISA7, ST6GAC2, TXNIP, FOS, and DCBLD2). The SHISA7, ST6GAC2, TXNIP, FOS, and DCBLD2 genes that may be viable therapeutic targets for the prevention or treatment of POAG, and regulated by the TFs (TGIF2, HNF1A, TCF3, and FOS).

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“…Die microRNAs regulieren zu etwa 20-30 % der Gene im menschlichen Genom [83] und spielen eine wichtige Rolle in der Genregulation. In den letzten Jahren wurde nachgewiesen, dass sie bei neurodegenerativen Erkrankungen eine wichtige Rolle spielen [84] und es wurden auch Assoziationen mit dem POWG gefunden [85,86]. Dabei zeigte die microRNA miR-17-5 p unter experimentellen Bedingungen, dass sie die Proliferation und Apoptose in humanen Trabekelwerkzellen steuert [87].…”

Section: Dysregulation Der Micrornaunclassified

Sekundäre Neuroprotektion beim Glaukom durch ergänzende medikamentöse Therapiekonzepte

Erb

2020

Klin Monatsbl Augenheilkd

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ZusammenfassungDas primäre Offenwinkelglaukom (POWG) wird derzeit als eine neurodegenerative Systemerkrankung angesehen. Die alleinige individualisierte Augeninnendrucksenkung wird dabei dem komplexen Geschehen im chronischen Verlauf der Erkrankung nicht gerecht werden, sodass begleitende medikamentöse Therapiekonzepte sinnvoll sind. Anhand von 4 Therapiestrategien, wie die Verbesserung der mitochondrialen Atmungskette mit Coenzym Q10, die Stabilisierung der mitochondrialen und zellulären Plasmamembranen mit Citicolin, die Verminderung des oxidativen Stresses am Auge und im Körper mit Curcumin und die Verbesserung des Fettstoffwechsels, speziell des LDL-Cholesterins, mit der Anwendung der Statine, soll ein Einblick in mögliche additive Therapieansätze gegeben werden. Da neuroprotektive Therapien als Monotherapien wenig erfolgversprechend sein dürften, werden sie eher in der Kombination aus verschiedenen Therapieansätzen bestehen.

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Relationship between the Pathogenesis of Glaucoma and miRNA

Cited by 41 publications

References 54 publications

miR‑17‑5p regulates the proliferation and apoptosis of human trabecular meshwork cells by targeting phosphatase and tensin homolog

miR‑17‑5p regulates the proliferation and apoptosis of human trabecular meshwork cells by targeting phosphatase and tensin homolog

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

Sekundäre Neuroprotektion beim Glaukom durch ergänzende medikamentöse Therapiekonzepte

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