The long non-coding RNA and its binding partner PTBP1 regulate exon 5 skipping of transcripts in group 4 medulloblastomas.

Background: Although some of the regulatory genes, signaling pathways, and gene regulatory networks altered in medulloblastomas (MB) are known, the roles of non-coding RNAs, particularly long non-coding RNAs (lncRNAs), are poorly described. Here we report that the lncRNA () gene is upregulated in group 4 medulloblastoma (G4 MB).

Methods: expression was assessed in MB subgroup patient-derived xenografts, cell lines, and patient samples. The effect of hemizygous deletion on proliferation, invasion, apoptosis, and colony formation were assessed in vitro and on tumor growth in vivo. dChIRP pull-down assays were used to assess binding partners, confirmed by immunoprecipitation. ΔE5 transcripts were examined in cell lines and publicly available RNA-seq data. Pathway analysis was performed by phospho-kinase profiling and RNA-seq.

Results: CRISPR/Cas9 deletion of reduced cell viability and invasion and increased apoptosis in G4 MB cell lines in vitro. hemizygous-deleted G4 MB cells injected into mouse cerebellums produced smaller tumors than those derived from parental cells expressing both copies of . lncRNA bound to the intronic region of the pre-mRNA transcript. also interacted with PTPB1 protein to regulate exon skipping to produce an aberrant protein. -driven regulation enhanced the expression of EGFR pathway genes in G4 MB cell lines and activated cell coagulation/hemostasis-related gene expression, suggesting a novel oncogenic role in G4 MB.

Conclusions: These results demonstrate the importance of lncRNA as a promoter of G4 MB and the role of the axis as an important oncogenic regulator in MB.