Unveiling Enhancer RNAs in Gliomas: A Systematic Review and Qualitative Synthesis

Area of Science:

• Neuro-oncology
• Molecular Biology
• Genomics

Background:

• Enhancer RNAs (eRNAs) are non-coding RNAs transcribed from enhancers, regulating gene expression, tumor progression, and treatment response.
• The role of eRNAs in glioma biology, including tumorigenesis, chemoresistance, and prognosis, is an emerging area of research.

Purpose of the Study:

• To systematically review and synthesize current evidence on the involvement of eRNAs in glioma.
• To elucidate the significance of eRNAs in gliomagenesis, temozolomide (TMZ) resistance, and patient survival outcomes.

Main Methods:

• A systematic review was conducted following PRISMA 2020 guidelines, searching PubMed/MEDLINE and Scopus databases.
• Included studies analyzed eRNAs in gliomas, assessing associations with tumorigenicity, survival, or TMZ resistance.
• Risk of bias was evaluated using ROBINS-I (Version 2), and findings were synthesized qualitatively.

Main Results:

• Ten studies involving 22 unique eRNAs were included.
• Specific eRNAs (TMZR1-eRNA, LINC02454*) were found to modulate TMZ sensitivity via pathways involving STAT3, SORBS2, and DDR1.
• Prognostic analysis revealed 12 eRNAs associated with poor survival and 7 with favorable outcomes, particularly in low-grade gliomas. HOXDeRNA was identified as a promoter of gliomagenesis.

Conclusions:

• eRNAs are active regulators, not mere by-products, influencing glioma initiation, therapeutic resistance, and survival.
• eRNAs hold significant potential as prognostic biomarkers and therapeutic targets in glioma.
• Further validation in clinical cohorts and development of eRNA-directed therapies are warranted for precision neuro-oncology.