CircRNAs Regulate Senescence-Associated miRNAs in Gastric Cancer.

Abstract

Gastric cancer is closely associated with the aging process, with its incidence and mortality rates significantly increasing with age, peaking around 85 years. Despite advance-ments in treatment modalities, current diagnostic and therapeutic approaches remain insuffi-cient, resulting in persistently low five-year survival rates among patients. The expanding global population and the intensifying aging process are anticipated to exacerbate the global burden of gastric cancer further, underscoring the urgency of exploring novel therapeutic strat-egies. A complex relationship exists between gastric cancer and cellular senescence, although the precise mechanisms remain incompletely understood. Cellular senescence is prevalent in gastric cancer treatment, typically serving as a natural anti-tumor barrier by inhibiting the un-controlled proliferation and malignant transformation of cancer cells. However, prolonged cel-lular senescence may trigger the secretion of pro-inflammatory factors, thereby promoting tu-morigenesis and progression. A systematic analysis of existing research data has revealed sig-nificant intersections between therapeutic targets for gastric cancer and senescence-associated signaling pathways, suggesting that modulating these critical nodes may constitute a pivotal mechanism for exploring novel therapeutic strategies bridging gastric cancer treatment and se-nescence. Circular RNAs (circRNAs) have garnered considerable attention with the advance-ment of bioinformatics and high-throughput sequencing technologies. As key regulatory fac-tors, circRNAs can modulate microRNAs (miRNAs) through a "sponge adsorption" mecha-nism, thereby influencing the post-transcriptional modification of critical genes. Given their high structural stability and widespread distribution in vivo, circRNAs have emerged as ideal candidate molecules for biomarkers and therapeutic targets in gastric cancer. This review fo-cuses on the mechanisms by which circRNAs, through sponging miRNAs, regulate key nodes in therapeutic targets and senescence signaling pathways in gastric cancer.