Circ-UBR5: An exonic circular RNA and novel small nuclear RNA involved in RNA splicing

Area of Science:

• Molecular Biology
• Oncology
• RNA Biology

Background:

• Circular RNAs (circRNAs) are non-coding RNAs with diverse, often unknown, functions in cellular processes.
• Many circRNAs lack obvious functional phenotypes, necessitating further investigation into their roles.
• Non-small cell lung cancer (NSCLC) is a major health concern with ongoing research into novel biomarkers and therapeutic targets.

Purpose of the Study:

• To investigate the potential function of circ-UBR5, a circRNA with no apparent phenotype in NSCLC cells.
• To determine the expression levels of circ-UBR5 in NSCLC tissues and its correlation with clinical parameters.
• To identify proteins that bind to circ-UBR5 and elucidate its role in RNA processing.

Main Methods:

• Real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) to measure circ-UBR5 expression in paired tumor and adjacent non-tumor tissues from 59 NSCLC patients.
• Statistical analysis to correlate circ-UBR5 expression with clinicopathological features, including tumor differentiation.
• Human Protein Microarray (Huprot™ Protoarray) to identify circRNA-binding proteins.

Main Results:

• circ-UBR5 was significantly downregulated in NSCLC tissues compared to adjacent non-tumorous tissues (p < 0.001).
• circ-UBR5 expression levels correlated with tumor differentiation (p = 0.00126), suggesting its potential as an NSCLC differentiation index.
• circ-UBR5 was found to bind splicing regulatory factors QKI, NOVA1, and U1 snRNA in the nucleus.

Conclusions:

• circ-UBR5 may serve as a potential biomarker for NSCLC differentiation.
• circ-UBR5 is implicated in RNA splicing regulation through its interaction with key splicing factors.
• The study presents an efficient strategy for identifying circRNA-binding proteins using protein microarrays.