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Published on: March 1, 2019
Long Noncoding RNAs: Emerging Players in Medulloblastoma
Pietro Laneve1, Jessica Rea2, Elisa Caffarelli1
1Institute of Molecular Biology and Pathology, National Research Council, Rome, Italy.
Abstract:
Central Nervous System tumors are the leading cause of cancer-related death in children, and medulloblastoma has the highest incidence rate. The current therapies achieve a 5-year survival rate of 50-80%, but often inflict severe secondary effects demanding the urgent development of novel, effective, and less toxic therapeutic strategies. Historically identified on a histopathological basis, medulloblastoma was later classified into four major subgroups-namely WNT, SHH, Group 3, and Group 4-each characterized by distinct transcriptional profiles, copy-number aberrations, somatic mutations, and clinical outcomes. Additional complexity was recently provided by integrating gene- and non-gene-based data, which indicates that each subclass can be further subdivided into specific subtypes. These deeper classifications, while getting over the typical tumor heterogeneity, indicate that different forms of medulloblastoma hold different molecular drivers that can be successfully exploited for a greater diagnostic accuracy and for the development of novel, targeted treatments. Long noncoding RNAs are transcripts that lack coding potential and play relevant roles as regulators of gene expression in mammalian differentiation and developmental processes. Their cell type- and tissue-specificity, higher than mRNAs, make them more informative about cell- type identity than protein-coding genes. Remarkably, about 40% of long noncoding RNAs are expressed in the brain and their aberrant expression has been linked to neuro-oncological disorders. However, while their involvement in gliomas and neuroblastomas has been extensively studied, their role in medulloblastoma is still poorly explored. Here, we present an overview of current knowledge regarding the function played by long noncoding RNAs in medulloblastoma biology.
Insights
Long noncoding RNAs are crucial regulators of gene expression, especially in the brain. Their role in medulloblastoma, a leading childhood brain cancer, is under-explored but holds promise for targeted therapies.
Area of Science:
- Neuro-oncology
- Molecular Biology
- Genomics
Background:
- Medulloblastoma is the most common pediatric brain tumor and a leading cause of cancer-related death in children.
- Current therapies have limited efficacy and severe side effects, necessitating novel treatment strategies.
- Medulloblastoma classification has evolved from histopathology to molecular subgroups (WNT, SHH, Group 3, Group 4) and subtypes, revealing tumor heterogeneity and distinct molecular drivers.
Purpose of the Study:
- To provide an overview of the current knowledge on the function of long noncoding RNAs (lncRNAs) in medulloblastoma biology.
- To highlight the potential of lncRNAs as diagnostic markers and therapeutic targets in medulloblastoma.
- To emphasize the need for further research into the role of lncRNAs in this pediatric brain cancer.
Main Methods:
- Literature review and synthesis of existing research on lncRNAs and medulloblastoma.
- Analysis of transcriptional profiles, copy-number aberrations, and somatic mutations in medulloblastoma subgroups.
- Integration of gene- and non-gene-based data to understand medulloblastoma complexity.
Main Results:
- Long noncoding RNAs are key regulators of gene expression, with high cell type and tissue specificity, particularly in the brain.
- Aberrant expression of lncRNAs is linked to neuro-oncological disorders, including gliomas and neuroblastomas.
- The specific role and function of lncRNAs in medulloblastoma remain largely unexplored compared to other brain tumors.
Conclusions:
- Long noncoding RNAs represent a promising area for developing novel, targeted therapies for medulloblastoma.
- Further investigation into lncRNA functions can improve diagnostic accuracy and therapeutic strategies for pediatric brain tumors.
- Understanding lncRNA dysregulation is crucial for advancing medulloblastoma treatment and improving patient outcomes.
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