The regulatory role and clinical application prospects of circRNA in the occurrence and development of CNS tumors

CNS Neuroscience & Therapeutics, 2024 · DOI: 10.1111/cns.14500 · Published: January 1, 2024

Simple Explanation

Central nervous system (CNS) tumors, originating from the brain or spinal cord, have high mortality rates despite aggressive treatment. Molecular mechanisms and risk factors remain unverified, complicating diagnosis and treatment. Circular RNAs (circRNAs), essential in CNS tumor development, perform critical biological functions. These include sponging to miRNAs, regulating gene transcription and splicing, interacting with proteins, encoding proteins/peptides, and expressing in exosomes. This review summarizes the molecular mechanism of circRNA in CNS tumors and explores potential clinical applications based on circRNA. It introduces advancements in clinical RNA-related technologies and discusses the therapeutic potential of circRNA in CNS tumors.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Review

Key Findings

1
CircRNAs participate in multiple molecular mechanisms of cellular normal or pathophysiology processes, especially as miRNA sponges in the cytoplasm, activating the modulation of target genes via miRNA response elements.
2
CircRNAs regulate transcription through various pathways, such as forming R-loops that affect transcription and mediating the activation of transcription factors.
3
Several studies have shown that circRNAs interacted with proteins, controlling cellular activity and interacting with specific RBPs. CircRNAs are also widely expressed in exosomes, playing roles in tumor progression, metabolic regulation, immune response, and treatment resistance.

Research Summary

CNS tumors are complex diseases with specific pathogeneses not fully understood and poor prognosis, often resistant to therapies. ncRNAs, including circRNAs, significantly contribute to tumor initiation and development. Circular RNAs are more expressed in the CNS and involved in pathological and physiological processes associated with CNS tumors. Current studies focus on circRNA in gliomas, suggesting upregulated circRNA may be more clinically significant. RNA-based therapeutic approaches have grabbed more attention, overcoming initial skepticism with various RNA modifying, packaging, and delivery systems. NcRNA-based drugs are widely studied as new therapeutic targets with many properties, making them potentially therapeutic molecules.

Practical Implications

Diagnostic Biomarkers

CircRNAs can be used as biomarkers for the diagnosis and prognosis of CNS tumors, particularly gliomas, due to their stable expression and potential to function as oncogenes or tumor inhibitors.

Therapeutic Targets

Modulating the expression of specific circRNAs can inhibit glioma development by targeting signaling pathways involved in tumorigenesis, such as Wnt, PI3K/AKT, JAK/STAT, and Notch pathways.

Immunotherapy and Chemotherapy

CircRNAs can be targeted to enhance the effectiveness of immunotherapy and chemotherapy in gliomas. For example, circRNAs can modulate PD-L1 expression to regulate immune escape or mediate TMZ sensitivity by regulating specific target genes.

Study Limitations

1
In vitro experiments may not always accurately represent physiological conditions.
2
Challenges in delivering circRNAs across cell membranes to exert pharmacological functions.
3
Need for improved pharmacokinetics and metabolic stability through chemical modifications.

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