Effect of intravitreal conbercept treatment on the expression of Long Noncoding RNAs and mRNAs in Proliferative Diabetic Retinopathy Patients
Effect of intravitreal conbercept treatment on the expression of Long Noncoding RNAs and mRNAs in Proliferative Diabetic Retinopathy Patients
复制标题
玻璃体内注射康柏西普治疗对增殖性糖尿病视网膜病变患者长非编码RNA和mRNA表达的影响
DOI：
10.1111/aos.14083
复制
发表时间：
2019-09-01
影响因子：
3.4
通讯作者：
Zhang, Han
中科院分区：
文献类型：
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作者：
Wang, Jiawei;Gao, Xue;Zhang, Han
目的探讨康柏西普对增殖性糖尿病视网膜病变（PDR）患者血管膜长链非编码RNA（lncRNA）和mRNA表达的影响。方法对20例PDR患者行玻璃体切割术（PPV）。10例患者接受PPV单独治疗（对照组），其他患者在PPV之前接受康柏西普注射（治疗组）。在手术过程中收获纤维血管膜。使用lncRNA阵列测试膜中lncRNA和mRNA的表达。通过生物信息学分析，确定差异表达基因的相关生物学模块和通路。构建lncRNA/mRNA共表达网络，以确定lncRNA和mRNA之间的相关性。实时荧光定量PCR验证芯片结果。结果共鉴定出427个差异表达的lncRNA，其中263个上调，164个下调。基因本体（GO）分析表明，这些lncRNA共表达的mRNA靶向于多种代谢过程，尤其是代谢产物的生成。京都基因与基因组百科全书（KEGG）结果表明，16种途径的基因表达存在显着差异，包括糖异生、HIF-1信号通路、NOD样受体途径等。lncRNA/mRNA共表达网络揭示了许多差异表达的lncRNA富集在HIF-1、TNF-alpha和NOD样受体途径中。LincRNA是最大的一类，进一步的生物信息学分析表明这些lincRNA共表达的mRNA主要参与PDR相关的生物学过程和病理通路。结论Conbercept治疗可改变PDR患者纤维血管膜中lncRNA和mRNA的表达谱。深入了解lncRNA与抗VEGF药物的关系，将有助于PDR的治疗。
Purpose To evaluate the effect of conbercept on the expression of long noncoding RNAs (lncRNAs) and mRNAs in the fibrovascular membranes of proliferative diabetic retinopathy (PDR) patients. Methods Twenty patients, diagnosed with PDR, who underwent pars plana vitrectomy (PPV), were recruited for this study. Ten patients were treated for PPV alone (Control Group), and the others received conbercept injections before PPV (Treated Group). The fibrovascular membranes were harvested during surgery. Expression of lncRNAs and mRNAs in the membranes was tested using lncRNA Arrays. Bioinformatics analyses were performed to identify the related biological modules and pathways of the differentially expressed genes. A lncRNA/mRNA coexpression network was built to identify the correlations between lncRNAs and mRNAs. Real-time PCR was conducted to verify the microarray results. Results We identified 427 differentially expressed lncRNAs, of which 263 were upregulated and 164 were downregulated. Gene ontology (GO) analysis indicated that these lncRNAs-coexpressed mRNAs targeted various metabolic processes, especially the gluconeogenesis. Kyoto Encyclopaedia of Genes and Genomes (KEGG) results indicated that 16 pathways had significant differences in gene expression, including gluconeogenesis, HIF-1 signalling pathway, NOD-like receptor pathway, etc. The lncRNA/mRNA coexpression network revealed that many differentially expressed lncRNAs were enriched in the HIF-1, TNF-alpha and NOD-like receptor pathways. LincRNAs were the largest category and further bioinformatics analysis implied that these lincRNAs-coexpressed mRNAs were mainly involved in PDR-related biological processes and pathological pathways. Conclusion Conbercept treatment can change the expression profiles of lncRNAs and mRNAs in the fibrovascular membranes of PDR patients. A complete understanding of the relationship between lncRNAs and anti-VEGF drugs may contribute to new therapeutic regimen for PDR.