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The Super Enhancer-Driven Long Noncoding RNA PRKCQ-AS1 Promotes Neuroblastoma Tumorigenesis by Interacting With MSI2

Sujanna Mondal1, Pei Y Liu1, Janith Seneviratne1

  • 1Children's Cancer Institute Australia and UNSW Centre for Childhood Cancer Research, University of New South Wales, Sydney, NSW, 2052, Australia.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|March 19, 2025
PubMed
Summary

This study identifies PRKCQ-AS1 as a key long noncoding RNA driving MYCN nonamplified neuroblastoma. Targeting the PRKCQ-AS1 and MSI2 protein interaction with small molecules offers a novel therapeutic strategy for neuroblastoma.

Keywords:
NeuroblastomaRNA binding proteinlong noncoding RNAlong noncoding RNA inhibitorsmall molecule compoundstumorigenesis

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Area of Science:

  • Oncology
  • Molecular Biology
  • RNA Biology

Background:

  • MYCN gene nonamplified neuroblastoma tumorigenesis drivers are poorly understood.
  • Long noncoding RNAs (lncRNAs) role in tumorigenesis is recognized, but therapeutic targeting with small molecules is underexplored.

Purpose of the Study:

  • To identify novel tumorigenic drivers in MYCN nonamplified neuroblastoma.
  • To investigate the therapeutic potential of targeting lncRNA-protein interactions with small molecules.

Main Methods:

  • Overexpression analysis of lncRNAs in neuroblastoma cell lines.
  • RNA immunoprecipitation and sequencing to identify RNA-protein interactions.
  • In vitro and in vivo studies to assess the functional impact of PRKCQ-AS1 and MSI2.
  • Compound screening to identify inhibitors of PRKCQ-AS1 and MSI2 interaction.

Main Results:

  • PRKCQ-AS1 is significantly overexpressed in MYCN nonamplified neuroblastoma and promotes proliferation by interacting with MSI2 protein.
  • This interaction stabilizes BMX mRNA, enhances ERK phosphorylation, and drives neuroblastoma progression.
  • PRKCQ-AS1 knockdown suppresses tumor growth in mice, and high PRKCQ-AS1/MSI2 levels correlate with poor patient outcomes.
  • NSC617570 effectively inhibits the PRKCQ-AS1-MSI2 interaction, reducing tumor progression in vitro and in vivo.

Conclusions:

  • PRKCQ-AS1 RNA interacts with MSI2 protein to drive MYCN nonamplified neuroblastoma tumorigenesis.
  • Targeting the PRKCQ-AS1-MSI2 interaction with small molecule compounds like NSC617570 represents a promising therapeutic strategy.