Dissecting the Pathogenesis of Diabetic Retinopathy Based on the Biological ceRNA Network and Genome Variation Disturbance

Author:

Zhu Xiaodan1ORCID,Hao Ming1ORCID,Yu Xinyang1ORCID,Lin Wenjian1ORCID,Ma Xuefei1ORCID,Xu Qian1ORCID,Cheng Lei2ORCID,Kuang Hongyu1ORCID

Affiliation:

1. Department of Endocrinology, The First Affiliated Hospital of Harbin Medical University, Harbin 150081, China

2. Department of Anesthesiology, The First Affiliated Hospital of Harbin Medical University, Harbin 150081, China

Abstract

Background. Diabetic retinopathy (DR) is the most important manifestation of diabetic microangiopathy. It is essential to explore the gene regulatory relationship and genomic variation disturbance of biological networks in DR progression. Methods. In this study, we constructed a comprehensive lncRNA-mRNA ceRNA network of DR procession (CLMN) and explored its topological characteristics. Results. Modular and functional analysis indicated that the organization of CLMN performed fundamental and specific functions in diabetes and DR pathology. The differential expression of hub ceRNA nodes and positive correlation reveals the highly connected ceRNA regulation and important roles in the regulating of DR pathology. A large proportion of SNPs in the TFBS, DHS, and enhancer regions of lncRNAs will affect lncRNA transcription and further cause expression variation. Some SNPs were found to disrupt the lncRNA functional elements such as miRNA target binding sites. These results indicate the complex nature of genotypic effects in the disturbing of CLMN and further contribute to gene expression variation and different disease phenotypes. Conclusion. The identification of individual genomic variations and analysis of biological network disturbance by these genomic variations will help provide more personalized treatment plans and promote the development of precision medicine for DR.

Funder

National Natural Science Foundation of China

Publisher

Hindawi Limited

Subject

Applied Mathematics,General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,Modeling and Simulation,General Medicine

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