Abstract

Glioblastoma (GBM) is the deadliest brain tumor. Its poor prognosis is due to cell heterogeneity, invasiveness, and high vascularization that impede an efficient therapeutic approach. In the past few years, several molecular links connecting GBM to neurodegenerative diseases (NDDs) were identified at preclinical and clinical level. In particular, giving the increasing critical role that epigenetic alterations play in both GBM and NDDs, we deeply analyzed the role of miRNAs, small non-coding RNAs acting epigenetic modulators in several key biological processes. Specific miRNAs, transported by extracellular vesicles (EVs), act as intercellular communication signals in both diseases. In this way, miRNA-loaded EVs modulate GBM tumorigenesis, as they spread oncogenic signaling within brain parenchyma, and control the aggregation of neurotoxic protein (Tau, Aβ-amyloid peptide, and α-synuclein) in NDDs. In this review, we highlight the most promising miRNAs linking GBM and NDDs playing a significant pathogenic role in both diseases.

Highlights

  • Glioblastoma recapitulates most of the hallmarks frequently described in cancer, such as uncontrolled proliferation, apoptosis resistance, dysregulated cell cycle, and angiogenesis

  • We evaluate the possible links between these dysregulated miRNAs with Alzheimer’s disease (AD) and Parkinson’s disease (PD), to determine potential molecular links for these diseases (Driver, 2014)

  • MiRNA338 was found to be upregulated in GBM, when compared to lower grades gliomas, and to promote tumor invasiveness by increasing the expression of MMP2 by downregulating t-shirt zinc finger homeobox (TSHZ) 3, a transcription factor involved in development (Li et al, 2018)

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Summary

Frontiers in Cellular Neuroscience

Specific miRNAs, transported by extracellular vesicles (EVs), act as intercellular communication signals in both diseases In this way, miRNA-loaded EVs modulate GBM tumorigenesis, as they spread oncogenic signaling within brain parenchyma, and control the aggregation of neurotoxic protein (Tau, Aβ-amyloid peptide, and α-synuclein) in NDDs. In this review, we highlight the most promising miRNAs linking GBM and NDDs playing a significant pathogenic role in both diseases.

INTRODUCTION
Neurodegenerative Diseases
Extracellular Vesicles
EVs Containing miRNAs in GBM Angiogenesis and Proliferation
EVs Containing miRNAs in GBM Migration and Invasion
Findings
CONCLUSION
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