CASC15-S Is a Tumor Suppressor lncRNA at the 6p22 Neuroblastoma Susceptibility Locus

• Published in: Cancer research (Chicago, Ill.) Ill.), 2015-08, Vol.75 (15), p.3155-3166
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Cell Differentiation - genetics; Cell Line, Tumor; Chromosomes, Human, Pair 6 - genetics; Gene Expression Regulation, Neoplastic; Genes, Tumor Suppressor; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Neuroblastoma - genetics; Neuroblastoma - mortality; Neuroblastoma - pathology; Polymorphism, Single Nucleotide; Reproducibility of Results; RNA, Long Noncoding - genetics
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.CAN-14-3613

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.