Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Hunan Clinical Research Center of Ophthalmic Disease, Changsha, Hunan, China.
Int J Med Sci. 2020 Jan 16;17(3):292-301. doi: 10.7150/ijms.37804. eCollection 2020.
Choroidal neovascularization (CNV) is a severe complication of the wet form of age-related macular degeneration (AMD). Long non-coding RNAs (lncRNAs) have been implicated in the pathogenesis of different ocular neovascular diseases. To identify the function and therapeutic potential of lncRNAs in CNV, we assessed lncRNAs and mRNA expression profile in a mouse model of laser-induced CNV by microarray analysis. The results of altered lncRNAs were validated by qRT-PCR. Bioinformatics analyses, including Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, were performed to clarify the potential biological functions and signaling pathways with which altered genes are most closely related. Moreover, to identify the interaction of lncRNAs and mRNAs, we constructed a coding-non-coding gene co-expression (CNC) network. By microarray analysis, we identified 716 altered lncRNAs and 821 altered mRNAs in CNV mice compared to controls. A CNC network profile based on 7 validated altered lncRNAs (uc009ewo.1, AK148935, uc029sdr.1, ENSMUST00000132340, AK030988, uc007mds.1, ENSMUST00000180519) as well as 282 interacted and altered mRNAs, and were connected by 713 edges. GO and KEGG analyses suggested that altered mRNAs, as well as those lncRNA-interacted mRNAs were enriched in immune system process and chemokine signaling pathway. Thus, lncRNAs are significantly altered in this mouse model of CNV and are involved in immunological regulation, suggesting that lncRNAs may play a critical role in the pathogenesis of CNV. Thus, dysregulated lncRNAs and their target genes might be promising therapeutic targets to suppress CNV in AMD.
脉络膜新生血管(CNV)是湿性年龄相关性黄斑变性(AMD)的严重并发症。长链非编码 RNA(lncRNA)已被牵连到不同的眼部新生血管疾病的发病机制中。为了确定 lncRNA 在 CNV 中的功能和治疗潜力,我们通过微阵列分析评估了激光诱导的 CNV 小鼠模型中的 lncRNA 和 mRNA 表达谱。通过 qRT-PCR 验证了改变的 lncRNA 的结果。进行了生物信息学分析,包括基因本体论(GO)分析和京都基因与基因组百科全书(KEGG)途径分析,以阐明与改变的基因最密切相关的潜在生物学功能和信号通路。此外,为了鉴定 lncRNA 和 mRNA 的相互作用,我们构建了编码-非编码基因共表达(CNC)网络。通过微阵列分析,我们在 CNV 小鼠中鉴定出与对照组相比有 716 个改变的 lncRNA 和 821 个改变的 mRNA。基于 7 个验证改变的 lncRNA(uc009ewo.1、AK148935、uc029sdr.1、ENS-MUST00000132340、AK030988、uc007mds.1、ENS-MUST00000180519)以及 282 个相互作用和改变的 mRNA,构建了 CNC 网络图谱,并通过 713 个边缘连接。GO 和 KEGG 分析表明,改变的 mRNA,以及那些与 lncRNA 相互作用的 mRNA,富集在免疫系统过程和趋化因子信号通路中。因此,在这种 CNV 的小鼠模型中,lncRNA 显著改变,并且参与免疫调节,表明 lncRNA 可能在 CNV 的发病机制中发挥关键作用。因此,失调的 lncRNA 和它们的靶基因可能是抑制 AMD 中 CNV 的有前途的治疗靶点。