Exosomal circ0000549 promotes MNNG-induced gastric cancer through miR-15b-5p/KIF1B

Sep 22, 2026

Accumulating evidence indicates that environmental exposures, especially to nitrites, critically influence the initiation and progression of gastric cancer. Exosomes function as mediators of intercellular communication during carcinogenesis. Exosomes derived from N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced transformed GES-1 cells and serum exosomes from patients with high-nitrite gastric cancer history affect normal cells and promote gastric cancer initiation. The study built a malignant transformation model, used bioinformatics to screen and validate circRNAs, and performed functional mechanistic experiments.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages19

Reading Time48 min

AccessFree to download

Introduction

Gastric cancer burden and precancerous lesions

Limitations of biomarkers and the role of dietary/nitrite exposures

MNNG as a chemical mutagen/carcinogen model

Prior pathways and the need for molecular mechanisms

circRNAs: characteristics and biogenesis

INTERNATIONAL JOURNAL OF MOLEcULAR MEdIcINE 57: 114, 2026 Exosomal circ0000549 promotes MNNG‑induced gastric cancer through miR‑15b‑5p/KIF1B ZHAOFENG LIANG 1,2* , ZIHAN GAO 1,2* , YUE ZHANG2 , JIAJIA SONG2 , HUI QIAN 1,2 and XUEZHONG XU 1 1 Wujin Institute of Molecular diagnostics and Precision cancer Medicine of Jiangsu University, Wujin Hospital Affiliated with Jiangsu University, Changzhou, Jiangsu 213017, P.R. China; 2Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. china Received August 20, 2025; Accepted February 12, 2026 dOI: 10.3892/ijmm.2026.5785 Abstract. Accumulating evidence indicates that environ‑ mental exposures, particularly to nitrites, play a critical role in the initiation and progression of gastric cancer (Gc) . during carcinogenesis, exosomes act as key mediators of intercellular communication . Exosomes derived from N‑methyl‑N'‑nitro‑N‑nitrosoguanidine (MNNG)‑induced malignantly transformed GES‑1 cells (TGES‑1), as well as serum exosomes from gastric cancer patients with a history of high nitrite exposure, were found to influence normal cells and promote Gc initiation. The present study established a malignant transformation model and applied bioinformatics analyses to screen and validate candidate circRNAs. A series of functional and mechanistic experiments were performed to elucidate the regulatory role of exosomes in Gc progression. circ0000549 was markedly upregulated in MNNG‑exposed GES‑1 cells, their derived exosomes and serum exosomes from patients with Gc. Further investigations revealed that circ0000549 overexpression enhanced GES‑1 cell malignant features, while also modulating epithelial‑mesenchymal transition and stemness‑related properties. Nude mouse exper‑ iments demonstrated that circ0000549, carried by malignantly transformed exosomes, plays a crucial role in MNNG‑induced gastric carcinogenesis . Mechanistically, miR‑15b‑5p was Correspondence to: Professor Xuezhong Xu, Wujin Institute of Molecular diagnostics and Precision cancer Medicine of Jiangsu University, Wujin Hospital Affiliated with Jiangsu University, 2 Yongning North Road, Changzhou, Jiangsu 213017, P.R. China E‑mail: [xuxuezhong@wjrmyy.cn](xuxuezhong@wjrmyy.cn) Professor Zhaofeng Liang, Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, 301 Xuefu Road, Zhenjiang, Jiangsu 212013, P.R. china E‑mail: [liangzhaofeng@ujs.edu.cn](liangzhaofeng@ujs.edu.cn) *contributed equally Key words: gastric cancer, exosome, circ0000549, chemical carcinogenesis, N‑methyl‑N'‑nitro‑N‑nitrosoguanidine, microRNA 15b‑5p identified as a potential target of circ0000549 . Circ0000549 functioned as a sponge for miR‑15b‑5p, leading to increased KIF1B expression and subsequent activation of the PI3K/AKT signaling pathway. collectively, these findings reveal that exosomal circ0000549 promotes malignant transformation of GES‑1 cells through the miR‑15b‑5p/KIF1B/PI3K/AKT axis. Exosomal circ0000549 may serve as a promising biomarker for Gc diagnosis and prognosis, highlighting its potential as a target for future therapeutic investigation. Introduction Gastric cancer (GC) is the fifth most frequently diagnosed malignancy worldwide and represents the fourth leading cause of cancer‑related mortality (1,2) . Precancerous lesions of Gc refer to pathological alterations of the gastric mucosa that exhibit a high propensity for malignant transforma‑ tion, involving multiple risk factors and multistep cellular changes (3) . In‑depth investigation of these precancerous lesions is essential for identifying key mechanisms underlying gastric carcinogenesis and provides critical evidence for early prevention and effective therapeutic intervention. Although advances in early screening and diagnostic technologies have been achieved in recent years, most patients with Gc are still diagnosed at advanced

FAQs

How do exosomes relate to gastric cancer progression in this study?

Exosomes are described as key mediators of intercellular communication during carcinogenesis, and exosomal cargo contributes to malignant transformation and gastric cancer initiation.

What did the researchers find about circ0000549 expression?

circ0000549 was markedly upregulated in MNNG-exposed GES-1 cells, their derived exosomes, and serum exosomes from gastric cancer patients.

Through which molecular axis does exosomal circ0000549 promote malignant transformation?

circ0000549 acts as a sponge for miR-15b-5p, increases KIF1B expression, and activates the PI3K/AKT signaling pathway, forming the miR-15b-5p/KIF1B/PI3K/AKT axis.

Sep 22, 2026

Upload by Valentina