Expression profiles of circRNAs, lncRNAs, and mRNAs in extreme phenotypes of diabetic retinopathy

Recent evidences highlighted regulatory role of circular RNAs (circRNAs) and long non-coding RNAs (lncRNAs) in the development of diabetic retinopathy (DR). However, the literatures and number of the RNAs identified were limited. Here, we compared the expression profiles of circRNAs, lncRNAs, and mRNAs in the blood of the susceptible individuals who developed severe DR within 5 years after being diagnosed with type 2 diabetic mellitus (T2DM), and the inherently resistant individuals who are spared from DR despite over 20-year history of T2DM. Using RNA microarray, hundreds of significantly differently expressed circRNAs, lncRNAs, and dozens of mRNAs were identified. Quantitative polymerase chain reaction verified the above findings. Gene ontology analysis indicated that the differentially expressed circRNAs were involved in platelet-derived growth factor binding, and mRNA and the cis-target genes of lncRNA participate in negative regulation of the Wnt signaling pathway. Kyoto Encyclopedia of Genes and Genomes pathway analysis suggested that the differentially expressed circRNAs were related to vitamin B6 metabolism and type 2 diabetes. The cis-target genes of lncRNAs are enriched in valine, leucine, and isoleucine biosynthesis and in the hypoxia-inducible factor-1 signaling pathway. The trans-target genes of lncRNAs are enriched in pathways such as vitamin B6 metabolism. Differentially expressed mRNAs are associated with type 2 diabetes and the vascular endothelial growth factor signaling pathway. Our findings demonstrate that circRNAs and lncRNAs may be involved in the regulation of DR and lay a foundation for further researches into the underlying mechanisms. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was supported by the National Natural Science Foundation of China (81570843; 81900866). ### Author Declarations All relevant ethical guidelines have been followed; any necessary IRB and/or ethics committee approvals have been obtained and details of the IRB/oversight body are included in the manuscript. Yes All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Available when appropriate request.