Abstract 6298: The novel long noncoding RNA lncNeur promotes neuroblastoma by up-regulating AURKA and Myc expression

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Abstract Background: Neuroblastoma is the most common solid tumor in early childhood, and accounts for approximately 15% of childhood cancer death. We have recently analyzed RNA sequencing data from 493 human neuroblastoma tissues, and identified the long noncoding RNA lincNeur as one of the transcripts, high expression of which most considerably correlated with poor prognosis in both MYCN oncogene-amplified and MYCN non-amplified neuroblastoma patients. Aims: To determine the tumorigenic role of lincNeur in neuroblastoma, and to identify the mechanism of action through which lincNeur exerts oncogenic function, also to screen for small molecule compound inhibitors of lincNeur. Methods and results: We performed RNA-binding protein pull-down assay and RNA-immunoprecipitation assay. RALY was identified and validated as one of the binding proteins of lincNeur. We also identified down-stream targets of lincNeur via genome-wide differential gene expression analysis. E2F1 and AURKA were identified as among the transcripts significantly down-regulated after lincNeur knockdown. RT-PCR and western blot analysis showed that lincNeur knockdown reduced E2F1 and AURKA mRNA and protein expression, and reduced N-Myc and c-Myc protein but not mRNA expression. In addition, lincNeur or RALY knockdown reduced, while over-expression of lincNeur or RALY promoted, neuroblastoma cell proliferation. We also demonstrated lincNeur knockdown significantly suppressed RALY protein binding to E2F1 and AURKA mRNAs. Mouse xenograft model experiment showed that lincNeur knockdown suppressed neuroblastoma tumor progression in vivo. Importantly, we have confirmed the binding site between lincNeur and RALY, and are screening small molecule compound libraries for inhibitors of lincNeur and RALY interaction for neuroblastoma therapy. Conclusions: The novel long noncoding RNA lincNeur promotes neuroblastoma by interacting with RALY to up-regulate E2F1 and AURKA mRNA and protein, as well as N-Myc and c-Myc protein expression. Small molecule compound inhibitors of lincNeur and RALY interaction is a promising therapeutic approach. Citation Format: Jing Wu, Pei Yan Liu, Belamy Cheung, Glenn Marshall, Marcel Dinger, Tao Liu. The novel long noncoding RNA lncNeur promotes neuroblastoma by up-regulating AURKA and Myc expression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6298.