The adrenergic-specific lncRNA NESPR regulates neuroblastoma cell viability and survival

Neuroblastoma is a childhood cancer of the sympathetic nervous system. Recent studies have shown that neuroblastoma tumors are composed of two cell identities, i.e. the adrenergic and mesenchymal identity. Both identities are driven by a core regulatory transcriptional circuitry, which acts as an autoregulatory positive feedforward loop, to delineate the cell identity through regulation of its target genes. We identified the long non-coding RNA NESPR to be specifically expressed in neuroblastoma cells of the adrenergic cell identity. NESPR expression correlates with several parameters of high-risk neuroblastoma and poor patient survival. We show that NESPR is contained within an insulated gene neighborhood with the adrenergic core regulatory transcription factor PHOX2B, and that NESPR regulates PHOX2B expression in cis. Knockdown of NESPR decreased neuroblastoma cell proliferation and induced cell death, highlighting NESPR’s importance in the survival of the adrenergic neuroblastoma cells.