2. Academic Validation
  3. Interventional effect of hesperetin on N-methyl-N'-nitro-N-nitrosoguanidine-induced exosomal circ008274 in affecting normal cells to promote gastric carcinogenesis

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

  • World J Gastroenterol. 2025 Apr 28;31(16):104920. doi: 10.3748/wjg.v31.i16.104920.
Zhao-Feng Liang 1 2,  Yu-Meng Xu 3,  Jia-Jia Song 3,  Zi-Han Gao 3,  Hui Qian 3,  Xue-Zhong Xu 1
Affiliations

Affiliations

  • 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. liangzhaofeng@ujs.edu.cn.
  • 3 Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang 212013, Jiangsu Province, China.
PMID: 40308800 DOI: 10.3748/wjg.v31.i16.104920
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.

Keywords

Circ0008274; Exosomes; Gastric cancer; Hesperetin; N-methyl-N’-nitro-N-nitrosoguanidine.

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