A Caltech Library Service

The long non-coding RNA SPRIGHTLY and its binding partner PTBP1 regulate exon 5 skipping of SMYD3 transcripts in group 4 medulloblastomas

Lee, Bongyong and Katsushima, Keisuke and Pokhrel, Rudramani and Yuan, Menglang and Stapleton, Stacie and Jallo, George and Wechsler-Reya, Robert J. and Eberhart, Charles G. and Ray, Animesh and Perera, Ranjan J. (2022) The long non-coding RNA SPRIGHTLY and its binding partner PTBP1 regulate exon 5 skipping of SMYD3 transcripts in group 4 medulloblastomas. Neuro-Oncology Advances, 4 . Art. No. vdac120. ISSN 2632-2498. PMCID PMC9569026. doi:10.1093/noajnl/vdac120.

Full text is not posted in this repository. Consult Related URLs below.

Use this Persistent URL to link to this item:


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 SPRIGHTLY (SPRY4-IT1) gene is upregulated in group 4 medulloblastoma (G4 MB). Methods. SPRIGHTLY expression was assessed in MB subgroup patient-derived xenografts, cell lines, and patient samples. The effect of SPRIGHTLY 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 SPRIGHTLY-binding partners, confirmed by immunoprecipitation. SMYD3 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 SPRIGHTLY reduced cell viability and invasion and increased apoptosis in G4 MB cell lines in vitro. SPRIGHTLY hemizygous-deleted G4 MB cells injected into mouse cerebellums produced smaller tumors than those derived from parental cells expressing both copies of SPRIGHTLY. SPRIGHTLY lncRNA bound to the intronic region of the SMYD3 pre-mRNA transcript. SPRIGHTLY also interacted with PTPB1 protein to regulate SMYD3 exon skipping to produce an aberrant protein. SPRIGHTLY-driven SMYD3 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 SPRIGHTLY lncRNA as a promoter of G4 MB and the role of the SPRIGHTLY-SMYD3-PTPB1 axis as an important oncogenic regulator in MB.

Item Type:Article
Related URLs:
URLURL TypeDescription CentralArticle
Lee, Bongyong0000-0002-6370-393X
Katsushima, Keisuke0000-0001-7770-432X
Jallo, George0000-0001-9607-6867
Eberhart, Charles G.0000-0002-2910-9427
Ray, Animesh0000-0002-0120-5820
Perera, Ranjan J.0000-0002-5926-3687
Additional Information:This work was supported by the Schamroth Project funded by Ian’s Friends Foundation, Hough Family Foundation, and Susan and Robb Hough to Ranjan J. Perera and George Jallo, and NCI grant 1R37CA230400 to Ranjan J. Perera and Charles Eberhart.
Funding AgencyGrant Number
Ian’s Friends FoundationUNSPECIFIED
Hough Family FoundationUNSPECIFIED
PubMed Central ID:PMC9569026
Record Number:CaltechAUTHORS:20221024-125854800.28
Persistent URL:
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:117557
Deposited By: Research Services Depository
Deposited On:01 Nov 2022 23:54
Last Modified:01 Nov 2022 23:54

Repository Staff Only: item control page