Circular RNA circ KMT2E is up-regulated in diabetic cataract lenses and is associated with miR-204-5p sponge function

Abstract Covalently closed, single-stranded circular RNAs (circRNAs) are a class of newly discovered endogenous RNAs involved in the pathological process of various types of diseases through sponging microRNAs (miRNAs). However, the role of circRNAs in diabetic cataract (DC) is unclear. Our previous studies have demonstrated that miR-204-5p was expressed more lowly in DC than the normal controls, but whether it relates to the sponge function of circRNAs remains unknown. This study aimed to identify differentially expressed circRNAs in DC tissues and investigate the interaction between circRNAs and miR-204-5p in the development of cataract. RNA-sequencing based circRNA expression profiling was determined in DC lens tissues as well as transparent lens tissues, and 1063 circRNAs were significantly differentially expressed in the DC group compared to the normal control group ( p  ≤ 0.05, fold change ≥ 2.0). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were applied to predict the function of these differentially expressed circRNAs, and the top ten enriched GO entries and KEGG pathways were annotated. Expression levels of the two candidate circRNAs having conserved interaction with miR-204-5p were validated by qRT-PCR, showing that the change direction of these circRNAs was consistent with the RNA-sequencing data. Moreover, circKMT2E was up-regulated more than two folds in DC lens tissues compared with normal tissues, exhibiting an expression trend opposite to miR-204-5p. Bio-informatics analysis showed that there were totally four seed sequences of circKMT2E on hsa-miR-204-5p. Thus, we speculated that circKMT2E may function as a sponge molecule of miR-204-5p and play a role in the pathogenesis of DC. Although the exact mechanisms need further validation, our study found that the differentially expressed circRNAs was involved in the pathogenesis of DC, which can provide a new target for non-surgical treatment of DC.