Microarray Analysis of Long Non-Coding RNAs and Messenger RNAs in a Mouse Model of Oxygen-Induced Retinopathy

Lusi Zhang; Xiaolin Fu; Huilan Zeng; Jiang-Hui Wang; Yingqian Peng; Han Zhao; Jingling Zou; Liwei Zhang; Yun Li; Shigeo Yoshida; Yedi Zhou

doi:10.7150/ijms.31274

Microarray Analysis of Long Non-Coding RNAs and Messenger RNAs in a Mouse Model of Oxygen-Induced Retinopathy

Int J Med Sci. 2019 Apr 20;16(4):537-547. doi: 10.7150/ijms.31274. eCollection 2019.

Authors

Lusi Zhang^{1

2}, Xiaolin Fu^{1

2

3}, Huilan Zeng^{1

2}, Jiang-Hui Wang^{4

5}, Yingqian Peng^{1

2}, Han Zhao^{1

2}, Jingling Zou^{1

2}, Liwei Zhang^{1

2}, Yun Li^{1

2}, Shigeo Yoshida⁶, Yedi Zhou^{1

2}

Affiliations

¹ Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China.
² Hunan Clinical Research Center of Ophthalmic Disease, Changsha, Hunan 410011, China.
³ Department of Ophthalmology, Hainan Western Central Hospital, Danzhou, Hainan 571799, China.
⁴ Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia.
⁵ Ophthalmology, Department of Surgery, University of Melbourne, East Melbourne, Victoria, Australia.
⁶ Department of Ophthalmology, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan.

Abstract

Objective: Retinal neovascularization is a severe complication of many ocular diseases. To clarify the possible functions and therapeutic potential of long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) in retinal neovascularization, we assessed their expression profile in a mouse model of oxygen-induced retinopathy (OIR). Methods: Microarray analysis was performed to identify altered lncRNA and mRNA expressions between OIR and control mice. The microarray results were validated by qRT-PCR. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted to determine biological functions and signaling pathways of the altered or interacted mRNAs. A coding-non-coding gene co-expression (CNC) network was constructed to identify the interaction of lncRNAs and mRNAs. Results: We identified 198 up-regulated and 175 down-regulated lncRNAs (fold change≥2.0, P<0.05), respectively in OIR mice compared to control mice. We also identified 412 up-regulated and 127 down-regulated mRNAs (fold change≥2.0, P<0.05), respectively in OIR mice compared to control mice. GO and KEGG analyses suggested that altered mRNAs were enriched in immune system process, exopeptidase activity, ECM-receptor interaction and protein digestion and absorption. Four validated lncRNAs (ENSMUST00000165968, ENSMUST00000153785, ENSMUST00000134409, and ENSMUST00000154285) and the nearby coding gene pairs were analyzed. A CNC network profile based on those validated altered lncRNAs as well as 410 interacted mRNAs was composed of 509 connections. Moreover, the GO and KEGG analyses demonstrated that these interacted mRNAs mainly enriched in blood vessel development, angiogenesis, cell adhesion molecules and leukocyte transendothelial migration pathways. Conclusion: Our data highlight the utility of altered lncRNA and mRNA profiling in understanding the pathogenesis of ischemia-induced retinal neovascularization and further suggest that therapeutic potential of altered lncRNA for retinal neovascularization.

Keywords: angiogenesis; expression profile; lncRNA; mRNA; microarray; oxygen-induced retinopathy; retinal neovascularization.

MeSH terms

Animals
Disease Models, Animal
Gene Expression Regulation / genetics
Gene Ontology
Humans
Mice
Mice, Inbred C57BL
Oxygen / toxicity
RNA, Long Noncoding / genetics*
RNA, Long Noncoding / isolation & purification
RNA, Messenger / genetics*
RNA, Messenger / isolation & purification
Retinal Neovascularization / chemically induced
Retinal Neovascularization / genetics*
Retinal Neovascularization / pathology
Signal Transduction / genetics

Substances

RNA, Long Noncoding
RNA, Messenger
Oxygen