Author:
Zhou Xiaoyu,Zhang Feng,Zhang Xinyue,Zhou Dengming,Zhao Yang,Chen Baihua,Duan Xuanchu
Abstract
Abstract
Background
Trabecular meshwork (TM) dysfunction-induced elevation of intraocular pressure has been identified as the main risk factor of irreversible optic nerve injury in Primary open‑angle glaucoma (POAG). Increasing evidences suggest that microRNA (miRNA) plays a vital role in the pathogenesis of POAG. This study aims to construct a miRNA-mRNA regulatory network and identify biomarkers for POAG.
Methods
miRNAs and mRNAs expression profiling of TM samples from controls and POAG patients were assessed through microarray analysis. Target genes of differentially expressed miRNAs (DEmiRNAs) were predicted by miEAA and miRNet. Then GO and KEGG pathway analysis of differentially expressed mRNAs (DEmRNAs) were performed. PPI of top 30 hub genes was identified and miRNA-mRNA network was established by STRING database and Cytoscape software. GSE27276 and GSE105269 datasets were used to verify the expression of hub genes and to predict potential biomarkers in TM and aqueous humor (AH) for POAG, respectively. Finally, GSEA analysis was conducted to estimate the main signaling pathway of POAG pathogenesis.
Results
A total of 29 up-regulated and 7 down-regulated miRNAs, 923 up-regulated and 887 down-regulated mRNAs were identified in TM of POAG compared with controls. Target genes and DEmRNAs were mainly enriched in nitric oxide biosynthetic process, vasopressin-regulated water reabsorption, and so on. Through miRNA-mRNA network construction, top 30 hub genes were regulated by 24 DEmiRNAs. 8 genes were aberrantly expressed in dataset GSE27276. 3 genes (CREB1, CAPZA2, SLC2A3) and 2 miRNAs (miR-106b-5p, miR-15a-5p) were identified as potential biomarkers for POAG in TM and AH, respectively. GSEA analysis revealed that these 3 genes modulated POAG through different pathways.
Conclusion
In this study, construction of miRNA-mRNA network and identification of biomarkers provide a novel insight into the pathogenesis, early diagnosis and treatment for POAG.
Publisher
Springer Science and Business Media LLC
Subject
Genetics (clinical),Genetics
Reference32 articles.
1. Tham YC, Li X, Wong TY, Quigley HA, Aung T, Cheng CY. Global prevalence of glaucoma and projections of glaucoma burden through 2040: a systematic review and meta-analysis. Ophthalmology. 2014;121(11):2081–90.
2. Buffault J, Labbe A, Hamard P, Brignole-Baudouin F, Baudouin C. The trabecular meshwork: Structure, function and clinical implications. A review of the literature. J Fr Ophtalmol. 2020;43(7):e217–30.
3. Quigley HA, Broman AT. The number of people with glaucoma worldwide in 2010 and 2020. Br J Ophthalmol. 2006;90(3):262–7.
4. Guo R, Shen W, Su C, Jiang S, Wang J. Relationship between the pathogenesis of glaucoma and miRNA. Ophthalmic Res. 2017;57(3):194–9.
5. Paylakhi SH, Yazdani S, April C, Fan JB, Moazzeni H, Ronaghi M, Elahi E. Non-housekeeping genes expressed in human trabecular meshwork cell cultures. Mol Vis. 2012;18:241–54.