Analysis of shared ceRNA networks and related-hub genes in rats with primary and secondary photoreceptor degeneration

Jia Liang; Dong Fang; Fei Yao; Lu Chen; Zhenhua Zou; Xiangcheng Tang; Lujia Feng; Yijing Zhuang; Ting Xie; Pengxue Wei; Pengfeng Li; Huiyan Zheng; Shaochong Zhang

doi:10.3389/fnins.2023.1259622

Analysis of shared ceRNA networks and related-hub genes in rats with primary and secondary photoreceptor degeneration

Front Neurosci. 2023 Sep 21:17:1259622. doi: 10.3389/fnins.2023.1259622. eCollection 2023.

Authors

Jia Liang^#¹, Dong Fang^#¹, Fei Yao¹, Lu Chen¹, Zhenhua Zou¹, Xiangcheng Tang¹, Lujia Feng¹, Yijing Zhuang¹, Ting Xie¹, Pengxue Wei¹, Pengfeng Li¹, Huiyan Zheng¹, Shaochong Zhang¹

Affiliation

¹ Shenzhen Eye Hospital, Shenzhen Eye Institute, Jinan University, Shenzhen, Guangdong, China.

^# Contributed equally.

Abstract

Introduction: Photoreceptor degenerative diseases are characterized by the progressive death of photoreceptor cells, resulting in irreversible visual impairment. However, the role of competing endogenous RNA (ceRNA) in photoreceptor degeneration is unclear. We aimed to explore the shared ceRNA regulation network and potential molecular mechanisms between primary and secondary photoreceptor degenerations.

Methods: We established animal models for both types of photoreceptor degenerations and conducted retina RNA sequencing to identify shared differentially expressed long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and messenger RNAs (mRNAs). Using ceRNA regulatory principles, we constructed a shared ceRNA network and performed function enrichment and protein-protein interaction (PPI) analyses to identify hub genes and key pathways. Immune cell infiltration and drug-gene interaction analyses were conducted, and hub gene expression was validated by quantitative real-time polymerase chain reaction (qRT-PCR).

Results: We identified 37 shared differentially expressed lncRNAs, 34 miRNAs, and 247 mRNAs and constructed a ceRNA network consisting of 3 lncRNAs, 5 miRNAs, and 109 mRNAs. Furthermore, we examined 109 common differentially expressed genes (DEGs) through functional annotation, PPI analysis, and regulatory network analysis. We discovered that these diseases shared the complement and coagulation cascades pathway. Eight hub genes were identified and enriched in the immune system process. Immune infiltration analysis revealed increased T cells and decreased B cells in both photoreceptor degenerations. The expression of hub genes was closely associated with the quantities of immune cell types. Additionally, we identified 7 immune therapeutical drugs that target the hub genes.

Discussion: Our findings provide new insights and directions for understanding the common mechanisms underlying the development of photoreceptor degeneration. The hub genes and related ceRNA networks we identified may offer new perspectives for elucidating the mechanisms and hold promise for the development of innovative treatment strategies.

Keywords: bioinformatics analysis; immune regulation; lncRNA-miRNA-mRNA networks; molecular mechanisms; photoreceptor degeneration.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by grants from the Sanming Project of Medicine in Shenzhen (grant number SZSM202011015); the Shenzhen Science and Technology Program (grant number KCXFZ20211020163813019); the Technology Innovation Talents Training Program (grant number RCBS20210706092347043); and the National Natural Science Foundation of China (grant number 81900877).