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Published on: May 30, 2025
The long noncoding RNA lncNB1 promotes tumorigenesis by interacting with ribosomal protein RPL35
Pei Y Liu1, Andrew E Tee1, Giorgio Milazzo2
1Children's Cancer Institute Australia for Medical Research, Randwick, NSW, 2031, Australia.
Abstract:
The majority of patients with neuroblastoma due to MYCN oncogene amplification and consequent N-Myc oncoprotein over-expression die of the disease. Here our analyses of RNA sequencing data identify the long noncoding RNA lncNB1 as one of the transcripts most over-expressed in MYCN-amplified, compared with MYCN-non-amplified, human neuroblastoma cells and also the most over-expressed in neuroblastoma compared with all other cancers. lncNB1 binds to the ribosomal protein RPL35 to enhance E2F1 protein synthesis, leading to DEPDC1B gene transcription. The GTPase-activating protein DEPDC1B induces ERK protein phosphorylation and N-Myc protein stabilization. Importantly, lncNB1 knockdown abolishes neuroblastoma cell clonogenic capacity in vitro and leads to neuroblastoma tumor regression in mice, while high levels of lncNB1 and RPL35 in human neuroblastoma tissues predict poor patient prognosis. This study therefore identifies lncNB1 and its binding protein RPL35 as key factors for promoting E2F1 protein synthesis, N-Myc protein stability and N-Myc-driven oncogenesis, and as therapeutic targets.
Insights
A novel long noncoding RNA, lncNB1, is highly expressed in neuroblastoma and promotes cancer growth by stabilizing the N-Myc oncoprotein. Targeting lncNB1 offers a potential therapeutic strategy for this aggressive childhood cancer.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Neuroblastoma, a common childhood cancer, often involves MYCN oncogene amplification and N-Myc oncoprotein overexpression.
- High N-Myc levels are associated with poor patient prognosis and treatment resistance.
Purpose of the Study:
- To identify novel molecular targets in MYCN-amplified neuroblastoma.
- To investigate the role of the long noncoding RNA lncNB1 in neuroblastoma oncogenesis.
Main Methods:
- RNA sequencing analysis of neuroblastoma cell lines and tissues.
- lncNB1 knockdown experiments in vitro and in vivo.
- Analysis of protein synthesis and gene transcription pathways.
Main Results:
- lncNB1 is significantly overexpressed in MYCN-amplified neuroblastoma and across various cancers.
- lncNB1 interacts with ribosomal protein RPL35 to boost E2F1 synthesis, driving DEPDC1B transcription.
- DEPDC1B promotes ERK phosphorylation and N-Myc stabilization, crucial for neuroblastoma growth.
- lncNB1 knockdown inhibits neuroblastoma cell growth and causes tumor regression in mice.
- High lncNB1 and RPL35 levels correlate with poor patient outcomes.
Conclusions:
- lncNB1 is a key driver of MYCN-driven neuroblastoma oncogenesis.
- lncNB1 and RPL35 are essential for E2F1 synthesis and N-Myc stability.
- lncNB1 represents a promising therapeutic target for neuroblastoma treatment.
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