{"title":"橙皮素对n -甲基-n '-硝基-n -亚硝基胍诱导的外泌体circ008274影响正常细胞促进胃癌发生的干预作用","authors":"Zhao-Feng Liang, Yu-Meng Xu, Jia-Jia Song, Zi-Han Gao, Hui Qian, Xue-Zhong Xu","doi":"10.3748/wjg.v31.i16.104920","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Aim: </strong>To investigate the interventional role of hesperetin on N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced exosomes in inducing gastric carcinogenesis.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>Hesperetin exerted an interventional effect on the gastric carcinogenesis process, particularly through the modulation of exosomal circ0008274 and its interaction with miR-526b-5p.</p>","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":"31 16","pages":"104920"},"PeriodicalIF":4.3000,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12038528/pdf/","citationCount":"0","resultStr":"{\"title\":\"Interventional effect of hesperetin on N-methyl-N'-nitro-N-nitrosoguanidine-induced exosomal circ008274 in affecting normal cells to promote gastric carcinogenesis.\",\"authors\":\"Zhao-Feng Liang, Yu-Meng Xu, Jia-Jia Song, Zi-Han Gao, Hui Qian, Xue-Zhong Xu\",\"doi\":\"10.3748/wjg.v31.i16.104920\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Aim: </strong>To investigate the interventional role of hesperetin on N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced exosomes in inducing gastric carcinogenesis.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>Hesperetin exerted an interventional effect on the gastric carcinogenesis process, particularly through the modulation of exosomal circ0008274 and its interaction with miR-526b-5p.</p>\",\"PeriodicalId\":23778,\"journal\":{\"name\":\"World Journal of Gastroenterology\",\"volume\":\"31 16\",\"pages\":\"104920\"},\"PeriodicalIF\":4.3000,\"publicationDate\":\"2025-04-28\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12038528/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"World Journal of Gastroenterology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.3748/wjg.v31.i16.104920\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"GASTROENTEROLOGY & HEPATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"World Journal of Gastroenterology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3748/wjg.v31.i16.104920","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}
Interventional effect of hesperetin on N-methyl-N'-nitro-N-nitrosoguanidine-induced exosomal circ008274 in affecting normal cells to promote gastric carcinogenesis.
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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