Aberrant expression of long noncoding RNAs in early diabetic retinopathy.

PURPOSE: Long noncoding RNAs (lncRNAs) are broadly classified as transcripts longer than 200 nucleotides. lncRNA-mediated biology has been implicated in a variety of cellular processes and human diseases. Diabetic retinopathy (DR) is one of the leading causes of blindness. However, little is known about the role of lncRNAs in DR The goal of this study aimed to identify lncRNAs involved in early DR and characterize their roles in DR pathogenesis.

METHODS: We established a mouse model of streptozotocin (STZ)-induced diabetes, and performed lncRNA expression profiling of retinas using microarray analysis. Based on the Pearson correlation analysis, an lncRNA/mRNA coexpression network was constructed. Gene ontology (GO) enrichment and KEGG analysis of lncRNAs-coexpressed mRNAs was conducted to identify the related biological modules and pathologic pathways. Real-time PCR was conducted to detect the expression pattern of lncRNA in the clinical samples and the RF/6A cell model of hyperglycemia.

RESULTS: Approximately 303 lncRNAs were aberrantly expressed in the retinas of early DR, including 214 downregulated lncRNAs and 89 upregulated lncRNAs. GO analysis indicated that these lncRNAs-coexpressed mRNAs were targeted to eye development process (ontology: biological process), integral to membrane (ontology: cellular component), and structural molecule activity (ontology: molecular function). Pathway analysis indicated that lncRNAs-coexpressed mRNAs were mostly enriched in axon guidance signaling pathway. In addition, MALAT1, a conserved lncRNA, was significantly upregulated in an RF/6A cell model of hyperglycemia, in the aqueous humor samples, and in fibrovascular membranes of diabetic patients.

CONCLUSIONS: lncRNAs are involved in the pathogenesis of DR through the modulation of multiple pathogenetic pathways. MALAT1, a conserved lncRNA, may become a potential therapeutic target for the prognosis, diagnosis, and treatment of DR.