Construction of miRNA-mRNA regulatory network indicates potential biomarkers for primary open-angle glaucoma

BMC Medical Genomics · 7 authors, 4 centres

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TL;DR

This study used microarray analysis of trabecular meshwork tissue to construct a miRNA-mRNA regulatory network and identify potential biomarkers for primary open-angle glaucoma. The analysis identified three genes (CREB1, CAPZA2, SLC2A3) as potential biomarkers in tissue and two miRNAs (miR-106b-5p, miR-15a-5p) as potential biomarkers in aqueous humor.

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Bioinformatics analyses were used to construct a regulatory network, identify differentially expressed molecules, and predict biomarkers. Three hub genes (CREB1, CAPZA2, SLC2A3) were highlighted as potential tissue biomarkers, and two miRNAs (miR-106b-5p, miR-15a-5p) were identified as potential biomarkers in aqueous humor with superior diagnostic accuracy. Limitations include small sample size, potential clinical confounding factors, and the lack of functional validation like PCR or luciferase assays.

STUDY TYPE

other

SPECIALTY

ophthalmology

SUMMARISED BY

AI pipeline

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100% · A

ORIGINAL PAPER

PMC10634160

Construction of miRNA-mRNA regulatory network indicates potential biomarkers for primary open-angle glaucoma

BMC Medical Genomics

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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. Supplementary Information The online version contains supplementary material available at 10.1186/s12920-023-01698-2.

CITATION EXPORT

Xiaoyu Zhou, Feng Zhang, Xinyue Zhang et al.. Construction of miRNA-mRNA regulatory network indicates potential biomarkers for primary open-angle glaucoma. BMC Medical Genomics. (2023). https://doi.org/10.1186/s12920-023-01698-2

AUTHORS

7 · 4 CENTRES

Xiaoyu Zhou, Feng Zhang, Xinyue Zhang, Dengming Zhou, Yang Zhao, Baihua Chen, Xuanchu Duan

1Aier Glaucoma Institute, Changsha Aier Eye Hospital, Changsha, Hunan Province China
2grid.452708.c0000 0004 1803 0208The Second Xiangya Hospital, Central South University, Changsha, Hunan Province China
3grid.216417.70000 0001 0379 7164The Third Xiangya Hospital, Central South University, Changsha, Hunan Province China
4https://ror.org/00f1zfq44grid.216417.70000 0001 0379 7164Aier School of Ophthalmology, Central South University, Changsha, Hunan Province China