Translation role of circRNAs in cancers

Area of Science:

• Molecular Biology
• Genomics
• RNA Biology

Background:

• Circular RNAs (circRNAs) are covalently closed RNA molecules identified through high-throughput sequencing.
• Emerging evidence suggests circRNAs possess translational capabilities, independent of traditional cap-dependent mechanisms.
• Internal ribosome entry sites (IRES) and N6-methyladenosine (m6A) modification are key regulators of cap-independent translation.

Purpose of the Study:

• To review the mechanisms of cap-independent translation mediated by circRNAs.
• To describe molecular methods for verifying circRNA translation.
• To summarize the roles of circRNA-encoded proteins in human cancers.

Main Methods:

• Bioinformatic analysis using databases like CircRNADb, CircBase, IRESite, and IRESbase to assess structural translation potential.
• Experimental validation using circRNA minigene reporter systems with green fluorescent protein (GFP).
• Literature review of studies reporting proteins encoded by specific circRNAs (e.g., circFBXW7, circAKT3) and their functions.

Main Results:

• Bioinformatic tools and databases confirm structural features supporting circRNA translation.
• Reporter assays demonstrate the translation potential of circRNAs.
• Several circRNA-derived proteins (e.g., circFBXW7, circMAPK1) have verified roles in various human cancers, including breast, colon, and glioblastoma.

Conclusions:

• CircRNAs can be translated through IRES-dependent and m6A-mediated pathways.
• Molecular techniques confirm the translational capacity of circRNAs.
• CircRNA-encoded proteins represent a novel class of functional molecules with significant implications in human cancer pathogenesis.