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Russell, Mike R; Penikis, Annalise; Oldridge, Derek A; Alvarez-Dominguez, Juan R; McDaniel, Lee; Diamond, Maura; Padovan, Olivia; Raman, Pichai; Li, Yimei; Wei, Jun S; Zhang, Shile; Gnanchandran, Janahan; Seeger, Robert; Asgharzadeh, Shahab; Khan, Javed; Diskin, Sharon J; Maris, John M; Cole, Kristina A
Cancer research (Chicago, Ill.), 08/2015, Letnik: 75, Številka: 15Journal Article
Chromosome 6p22 was identified recently as a neuroblastoma susceptibility locus, but its mechanistic contributions to tumorigenesis are as yet undefined. Here we report that the most highly significant single-nucleotide polymorphism (SNP) associations reside within CASC15, a long noncoding RNA that we define as a tumor suppressor at 6p22. Low-level expression of a short CASC15 isoform (CASC15-S) associated highly with advanced neuroblastoma and poor patient survival. In human neuroblastoma cells, attenuating CASC15-S increased cellular growth and migratory capacity. Gene expression analysis revealed downregulation of neuroblastoma-specific markers in cells with attenuated CASC15-S, with concomitant increases in cell adhesion and extracellular matrix transcripts. Altogether, our results point to CASC15-S as a mediator of neural growth and differentiation, which impacts neuroblastoma initiation and progression.
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in: SICRIS
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