Upregulated Circular RNAs in Gastric Cancer: Target Identification and Tools for Therapeutic Intervention

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Gastric cancer (GC) pathogenesis and dissemination involve complex molecular mechanisms.
• Circular RNAs (circRNAs) are increasingly recognized as critical regulators in various cancers, including GC.
• Understanding circRNA functions is crucial for developing novel therapeutic strategies.

Purpose of the Study:

• To identify upregulated circRNAs implicated in gastric cancer pathogenesis and dissemination.
• To investigate circRNA targets including transmembrane receptors, secreted proteins, RNA metabolism, ubiquitination, WNT signaling, ferroptosis, and druggable enzymes.
• To validate circRNAs as tools for identifying therapeutic targets for gastric cancer.

Main Methods:

• Comprehensive literature survey of PubMed database focusing on circRNAs in gastric cancer.
• Analysis of circRNA targets related to physiological processes and protein classes.
• Identification of circRNAs targeting pathways modulated by approved drugs for GC.

Main Results:

• Upregulated circRNAs involved in GC pathogenesis and dissemination were identified.
• Key target classes frequently affected by circRNAs include solute carrier (SLC) proteins, heterogeneous nuclear RNA (hnRNA) subtypes, and ubiquitin-specific proteases (USPs).
• CircRNAs targeting pathways of approved GC drugs like vascular endothelial growth factor A (VEGF-A) and programmed death-ligand 1 (PD-L1) were found, confirming circRNAs as target identification tools.

Conclusions:

• CircRNAs represent promising biomarkers and therapeutic targets in gastric cancer.
• Specific circRNAs modulate critical pathways such as WNT signaling and ferroptosis, and target druggable enzymes.
• Further research into the technical challenges of inhibiting these circRNAs and their targets is warranted for clinical translation.