Four Autophagy-Related Long Noncoding RNAs Provide Coexpression and ceRNA Mechanisms in Retinoblastoma through Bioinformatics and Experimental Evidence

[Image: see text] Retinoblastoma (RB) is the most common type of intraocular malignant tumor that lowers the quality of life among children worldwide. Long noncoding RNAs (lncRNAs) are reported to play a dual role in tumorigenesis and development of RB. Autophagy is also reported to be involved in RB occurrence. Although several studies of autophagy-related lncRNAs in RB have been explored before, there are still unknown potential mechanisms in RB. In the present study, we mined dataset GSE110811 from the Gene Expression Omnibus database and downloaded autophagy-related genes from the Human Autophagy Database for further bioinformatic analysis. By implementing the differential expression analysis and Pearson correlation analysis on the lncRNA expression matrix and autophagy-related genes expression matrix, we identified four autophagy-related lncRNAs (namely, N4BP2L2-IT2, SH3BP5-AS1, CDKN2B-AS1, and LINC-PINT) associated with RB. We then performed differential expression analysis on microRNA (miRNA) from dataset GSE39105 for further analyses of lncRNA–miRNA–mRNA regulatory mechanisms. With the miRNA–lncRNA module on the StarBase 3.0 website, we predicted the differentially expressed miRNAs that could target the autophagy-related lncRNAs and constructed a potential lncRNA–miRNA–mRNA regulatory network. Furthermore, the functional annotations of these target genes in regulatory networks were presented using the Cytoscape and the Metascape annotation tool. Finally, the expression pattern of the four autophagy-related lncRNAs was evaluated via qRT-PCR. In conclusion, our findings suggest that the four autophagy-related lncRNAs could be critical molecules associated with the development of RB and affect the occurrence and development of RB through the lncRNA–miRNA–mRNA regulatory network. Genes (GRP13B, IFT88, EPHA3, GABARAPL1, and EIF4EBP1) may serve as potential novel therapeutic targets and biomarkers in RB.