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

Abstract

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.

Comprehensive Analysis of Serum Small Extracellular Vesicles-Derived Coding and Non-Coding RNAs from Retinoblastoma Patients for Identifying Regulatory Interactions

“…Computational analysis of lncRNA-miRNA-mRNA interactions would provide a theoretical basis for the molecular mechanism of disease, and for the identification of potential therapeutic targets [ 92 ]. However, to our knowledge only a single study has demonstrated autophagy-related lncRNA-miRNA-mRNA regulatory networks in RB [ 93 ]. Thus, we investigated the direct interactions between lncRNA-miRNA, miRNA-mRNA and lncRNA-mRNA, and constructed lncRNA-miRNA-mRNA network.…”

A novel autophagy-related long non-coding RNAs prognostic risk score for clear cell renal cell carcinoma

“…Shao et al suggested that SH3BP5-AS1 may engage in natural killer cell-mediated cytotoxicity [ 40 ], which is directly regulated by autophagy [ 41 ]. Related studies have shown that abnormalities in the lncRNA SH3BP5-AS1 are associated with poor prognosis in patients with retinoblastoma by activating carcinogenic autophagy [ 42 ]. LncRNA SH3BP5-AS1 can also serve as a necroptosis-associated lncRNA and is included in the necroptosis-associated lncRNA model for predicting breast cancer prognosis [ 43 ].…”

Identifying Autophagy-Related lncRNAs and Potential ceRNA Networks in NAFLD

“…Over the past few years, significant inroads have been made in our understanding of the role of lncRNAs. The various functions of lncRNAs affect different aspects of physiology, such as cell cycle regulation, cell differentiation, gene post-transcriptional regulation and responses to diverse stresses and stimuli ( Chen et al, 2019 ; Zottel et al, 2020 ; Ren et al, 2021 ). LncRNAs can reportedly compete for miRNA binding, thereby modulating the expression of genes.…”