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The therapeutic and diagnostic potential of regulatory noncoding RNAs in medulloblastoma
Piyush Joshi1,2, Keisuke Katsushima1,2, Rui Zhou2
1Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, School of Medicine, Johns Hopkins University, Baltimore, Maryland.
Abstract:
Medulloblastoma, a central nervous system tumor that predominantly affects children, always requires aggressive therapy. Nevertheless, it frequently recurs as resistant disease and is associated with high morbidity and mortality. While recent efforts to subclassify medulloblastoma based on molecular features have advanced our basic understanding of medulloblastoma pathogenesis, optimal targets to increase therapeutic efficacy and reduce side effects remain largely undefined. Noncoding RNAs (ncRNAs) with known regulatory roles, particularly long noncoding RNAs (lncRNAs) and microRNAs (miRNAs), are now known to participate in medulloblastoma biology, although their functional significance remains obscure in many cases. Here we review the literature on regulatory ncRNAs in medulloblastoma. In providing a comprehensive overview of ncRNA studies, we highlight how different lncRNAs and miRNAs have oncogenic or tumor suppressive roles in medulloblastoma. These ncRNAs possess subgroup specificity that can be exploited to personalize therapy by acting as theranostic targets. Several of the already identified ncRNAs appear specific to medulloblastoma stem cells, the most difficult-to-treat component of the tumor that drives metastasis and acquired resistance, thereby providing opportunities for therapy in relapsing, disseminating, and therapy-resistant disease. Delivering ncRNAs to tumors remains challenging, but this limitation is gradually being overcome through the use of advanced technologies such as nanotechnology and rational biomaterial design.
Insights
Regulatory noncoding RNAs (ncRNAs), including long noncoding RNAs (lncRNAs) and microRNAs (miRNAs), play crucial roles in medulloblastoma, a pediatric brain tumor. Understanding these ncRNAs offers potential for targeted therapies against resistant disease.
Area of Science:
- Neuro-oncology
- Molecular Biology
- Genetics
Background:
- Medulloblastoma is a common pediatric central nervous system tumor requiring aggressive treatment.
- Despite advances in molecular subclassification, effective therapeutic targets for medulloblastoma remain elusive, contributing to high morbidity and mortality.
- Noncoding RNAs (ncRNAs), such as long noncoding RNAs (lncRNAs) and microRNAs (miRNAs), are implicated in medulloblastoma pathogenesis but their functional roles are not fully understood.
Purpose of the Study:
- To review the current literature on regulatory ncRNAs in medulloblastoma.
- To highlight the oncogenic or tumor-suppressive functions of various lncRNAs and miRNAs in medulloblastoma.
- To explore the potential of ncRNAs as theranostic targets for personalized medulloblastoma therapy.
Main Methods:
- Comprehensive literature review of studies investigating ncRNAs in medulloblastoma.
- Analysis of identified lncRNAs and miRNAs for their roles in tumor development and progression.
- Evaluation of ncRNA specificity to medulloblastoma subgroups and stem cells.
Main Results:
- Various lncRNAs and miRNAs exhibit either oncogenic or tumor-suppressive activities in medulloblastoma.
- Specific ncRNAs are associated with distinct medulloblastoma subgroups, suggesting potential for personalized treatment strategies.
- Several ncRNAs are identified as specific to medulloblastoma stem cells, which are linked to treatment resistance and metastasis.
Conclusions:
- Regulatory ncRNAs represent promising theranostic targets for medulloblastoma, particularly for overcoming therapeutic resistance.
- Exploiting subgroup-specific and stem cell-specific ncRNAs could lead to more effective and personalized treatment approaches.
- Advances in delivery technologies, like nanotechnology, are paving the way for therapeutic applications of ncRNAs in medulloblastoma.
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