Interventional effect of hesperetin on N-methyl-N'-nitro-N-nitrosoguanidine-induced exosomal circ008274 in affecting normal cells to promote gastric carcinogenesis.
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Abstract
Background: Hesperetin, a flavonoid predominantly present in citrus fruits, exhibits significant intervention effects on both the initiation and progression of gastric cancer. However, the specific mechanisms underlying this effect remain unclear.
Aim: To investigate the interventional role of hesperetin on N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced exosomes in inducing gastric carcinogenesis.
Methods: Bioinformatics technology was used to identify the critical molecular components underlying hesperetin-mediated inhibition of MNNG induced gastric carcinogenesis through exosomal circular RNA. Biological experiments were conducted to validate these findings.
Results: Exosomes derived from TGES-1 cells (TGES-1-EX) significantly enhanced the proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and stemness of GES-1 cells. The oncogenic potential of TGES-1-EX was significantly diminished following hesperetin pretreatment. TGES-1-EX with overexpressed or knocked down circ0008274 was extracted and GES-1 cells were treated in combination with hesperetin or alone. Our investigation revealed that hesperetin exerted significant inhibitory effects on MNNG-induced gastric carcinogenesis by exosomal circ0008274. Bioinformatics prediction identified microRNA (miR)-526b-5p as a potential miRNA binding to circ0008274. Functional experiments demonstrated that hesperetin may mediate its intervention in MNNG-induced gastric cancer initiation by targeting miR-526b-5p through exosomal circ0008274. TGES-1-EX circ0008274 promoted the proliferation, EMT, and cancer stem cell-like characteristics in GES-1 cells through miR-526b-5p-mediated regulatory mechanisms.
Conclusion: Hesperetin exerted an interventional effect on the gastric carcinogenesis process, particularly through the modulation of exosomal circ0008274 and its interaction with miR-526b-5p.
期刊介绍：
The primary aims of the WJG are to improve diagnostic, therapeutic and preventive modalities and the skills of clinicians and to guide clinical practice in gastroenterology and hepatology.
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