Interventional effect of hesperetin on N-methyl-N’-nitro-Nnitrosoguanidine-induced exosomal circ008274 in affecting normal cells to promote gastric carcinogenesis  

作　　者：Zhao-Feng Liang Yu-Meng Xu Jia-Jia Song Zi-Han Gao Hui Qian Xue-Zhong Xu 

机构地区：[1]Wujin Institute of Molecular Diagnostics and Precision Cancer Medicine of Jiangsu University,Wujin Hospital Affiliated with Jiangsu University,Changzhou 213017,Jiangsu Province,China [2]Jiangsu Key Laboratory of Medical Science and Laboratory Medicine,School of Medicine,Jiangsu University,Zhenjiang 212013,Jiangsu Province,China

出　　处：《World Journal of Gastroenterology》2025年第16期66-88,共23页世界胃肠病学杂志(英文)

基　　金：Supported by the National Natural Science Foundation of China,No.81602883;Technology Development Project of Jiangsu University,No.20220516;Postgraduate Research and Practice Innovation Program of Jiangsu Province,No.KYCX233765.

摘　　要：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-Nnitrosoguanidine(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.

关 键 词：HESPERETIN Gastric cancer N-methyl-N’-nitro-N-nitrosoguanidine EXOSOMES Circ0008274 

分 类 号：R735.2[医药卫生—肿瘤]