Splicing Dysregulation as Oncogenic Driver and Passenger Factor in Brain Tumors

Area of Science:

• Molecular Biology
• Oncology
• Neuroscience

Background:

• Brain tumors are diverse neoplasms with malignancy linked to gene expression reprogramming.
• Aberrant RNA processing, especially alternative splicing defects, is common in brain tumors.
• These defects arise from altered splicing factors or mutations in splicing machinery.

Purpose of the Study:

• To summarize current knowledge on splicing abnormalities in brain tumors.
• To elucidate how aberrant splicing contributes to brain tumor development and progression.
• To review emerging splicing-targeted cancer therapies for brain tumors.

Main Methods:

• Literature review of studies on splicing in brain tumors.
• Analysis of mechanisms linking splicing defects to cancer hallmarks.
• Overview of current and developing splicing-targeted therapeutic strategies.

Main Results:

• Splicing abnormalities contribute to sustained proliferative signaling, evasion of growth suppressors, and tumor microenvironment modulation (angiogenesis, intercellular communication).
• Dysfunctional proteins from aberrant splicing alter fundamental cellular processes, promoting brain tumor growth.
• Oligonucleotide-based and chemical modulator approaches are being developed to target alternative splicing in brain tumors.

Conclusions:

• Alternative splicing is a critical factor in brain tumor heterogeneity and progression.
• Targeting splicing mechanisms offers a promising avenue for novel brain tumor therapies.
• Further research into splicing-targeted interventions could significantly impact brain tumor treatment outcomes.