Identification of non-coding RNAs and their functional network associated with optic nerve invasion in retinoblastoma

Optic nerve invasion (ONI) is an important high-risk feature and prognostic indicator of retinoblastoma (RB). Emerging evidence has revealed that non-coding RNAs (ncRNAs) play important roles in tumor perineural invasion (PNI). Nevertheless, the regulatory role of ncRNAs in the ONI of RB is poorly understood. In the current study, whole-transcriptome sequencing was performed to assess the expression profiles of ncRNAs and mRNAs in RB tissues, with or without ONI. Based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, we predicted the biological functions of differentially expressed (DE) mRNAs. We then constructed competing endogenous RNA (ceRNA) regulatory networks based on bioinformatics analysis. The hsa_circ_0015965/lncRNA MEG3-hsa-miR-378a-5p-NOTCH1 pathway was selected and validated by real-time qPCR, western blotting, and dual luciferase reporter assays. Moreover, we demonstrated that NOTCH1 promotes the malignant progression of RB. Taken together, our results provide novel insights into the mechanism underlying optic nerve invasion in RB.