The Role of Circular RNAs in Chemoresistance of Gastric Cancer: Mechanisms and Therapeutic Potential
The Role of Circular RNAs in Chemoresistance of Gastric Cancer: Mechanisms and Therapeutic Potential
Shima Hasani,1,*
1. Department of Animal Biology, Faculty of Natural Sciences, The University of Tabriz, Tabriz, Iran.
Introduction: Chemoresistance remains a significant challenge in the treatment of gastric cancer, leading to poor patient outcomes. Circular RNAs (circRNAs) have recently emerged as crucial regulators of chemoresistance. This review aims to explore the mechanisms by which circRNAs contribute to chemoresistance in gastric cancer and to discuss their potential as therapeutic targets.
Methods: A comprehensive literature review was performed using databases such as PubMed, Scopus, and Web of Science. Studies focusing on the involvement of circRNAs in gastric cancer chemoresistance were identified, and relevant data were extracted and synthesized.
Results: CircRNAs significantly contribute to chemoresistance in gastric cancer through various mechanisms. For instance, circRNA CDR1as contributes to cisplatin resistance by sponging miR-138-5p and upregulating EZH2. Similarly, circ_0006528 enhances 5-fluorouracil resistance by sponging miR-7-5p and upregulating EGFR expression. CircAKT3 mediates doxorubicin resistance through miR-198 sponging and subsequent upregulation of PIK3R1. Additionally, circRNA_100269 reduces cisplatin sensitivity by acting as a miR-630 sponge, resulting in increased IGF1R expression, while circ_0026359 promotes oxaliplatin resistance via sponging miR-1200 and upregulating FOXM1. Beyond miRNA sponging, circRNAs can modulate drug transporters and apoptosis pathways. For example, circABCB10 is involved in drug resistance by upregulating ABCB10 transporter expression, enhancing drug efflux. CircMCTP2 contributes to chemoresistance by inhibiting apoptosis through the regulation of the Bcl-2/Bax ratio. CircRNA_101237 has been shown to activate the Wnt/β-catenin signaling pathway, leading to enhanced cell survival and drug resistance. Additionally, circRNA_104916 mediates resistance by promoting autophagy, allowing cancer cells to survive under chemotherapeutic stress. These diverse mechanisms underline the critical role of circRNAs in gastric cancer chemoresistance.
Conclusion: CircRNAs play critical roles in mediating chemoresistance in gastric cancer through mechanisms such as miRNA sponging and modulation of key signaling pathways. Understanding these mechanisms provides insights into potential therapeutic strategies to overcome chemoresistance. Targeting circRNAs may offer a promising approach to enhance the efficacy of chemotherapy in gastric cancer patients.