Global lncRNA expression profiles in medulloblastoma reveal crucial lncRNA-oncogene interactions in Sonic hedgehog

Iván Martínez de Estíbariz1, Unai Illarregi1, Daniel Sinnett2,3

  • 1Department of Genetics, Physical Anthropology and Animal Physiology, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), Leioa, Spain.

Neuro-Oncology Advances
|October 30, 2025
PubMed
Abstract

Insights

This study identifies specific long noncoding RNAs (lncRNAs) as potential biomarkers for medulloblastoma (MB) molecular groups. These lncRNAs, including Lnc-SMARCA2, MGC32805, and LOC107986446, are linked to specific MB subtypes and oncogenes, offering new therapeutic targets.

Area of Science:

  • Genomics
  • Molecular Biology
  • Oncology

Background:

  • Medulloblastoma (MB) characterization is improving with multi-omic studies, but novel molecular biomarkers are needed.
  • Current profiling focuses on the protein-coding genome, leaving noncoding regions unexplored.
  • Long noncoding RNAs (lncRNAs) are emerging as crucial regulators in MB and potential key biomarkers.

Purpose of the Study:

  • To identify lncRNAs specific to MB molecular groups.
  • To explore the role of lncRNAs in MB pathogenesis and disease mechanisms.
  • To enhance understanding of MB's genomic landscape through noncoding region analysis.

Main Methods:

  • RNA-sequencing (RNA-seq) data from 261 MB patients (54 Spanish, 207 public).
  • Expression analysis and Weighted Gene Coexpression Network (WGCNA) to identify lncRNA-oncogene interactions.
  • Examination of group-specific interactions to infer pathogenic roles.

Main Results:

  • LncRNA expression profiles identified 4 clusters corresponding to MB molecular groups.
  • Group-specific lncRNAs were found for Sonic hedgehog (SHH), Group 3 (Gr3), and Group 4 (Gr4) MB.
  • Lnc-SMARCA2 (SHH), MGC32805/LOC107986446 (Gr4), and a 5-lncRNA signature (Gr3) were identified and linked to specific oncogenes and pathways.

Conclusions:

  • Lnc-SMARCA2, MGC32805, and LOC107986446 are exclusively deregulated in SHH and Gr4 MB, respectively.
  • These lncRNAs are associated with group-specific MB oncogenes, indicating their role in pathogenesis.
  • These findings highlight promising novel biomarkers and therapeutic targets for MB treatment.

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