Jiang Wei, Lu Wei, Liu Jun, Ren Haixia, Zhao Xuequn, Yang Wenjie
Department of Infectious Diseases, Tianjin First Central Hospital, China.
Liver Cancer Center, Tianjin Medical University Cancer Institute & Hospital, China.
Toxicol Lett. 2024 Feb;392:64-74. doi: 10.1016/j.toxlet.2024.01.002. Epub 2024 Jan 4.
Studying the regulatory mechanism of gastric disease progression to gastric cancer (GC) is essential. miR-520f expression is down-regulated in GC and inhibits the proliferation of gastric cancer cells, suggesting that it is associated with the development of GC, but whether it plays a role in the gastric precancerous lesion (GPL) is unclear. This study aimed to investigate the effect of miR-520f-3p in the N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced GPL model and to elucidate the role of its downstream target gene Kruppel-like factor 7 (KLF7) in it. The experimental results showed that miR-520f-3p expression was down-regulated in the MNNG-induced GES-1 cell model, and overexpression of miR-520f-3p reversed the effects of MNNG on cell migration, invasion and epithelial-mesenchymal transition (EMT) -related protein expression. Meanwhile, overexpression of KLF7 attenuated the effect of miR-520f-3p on GPL. In a mouse GPL model, it was observed that MNNG elicited inflammation and EMT processes in mouse gastric tissues through the KLF7/ Nuclear Factor Kappa B (NFκB) pathway, and silencing KLF7 alleviated MNNG-induced gastric epithelial cell injury and gastric atrophy symptoms. These results provide a new perspective for understanding the development of GPL, and the development of new therapies targeting miR-520f-3p and KLF7 may provide new ideas for the prevention and treatment of gastric cancer.
研究胃癌(GC)进展的调控机制至关重要。miR-520f在GC中的表达下调,并抑制胃癌细胞的增殖,这表明它与GC的发生发展有关,但它是否在胃癌前病变(GPL)中发挥作用尚不清楚。本研究旨在探讨miR-520f-3p在N-甲基-N'-硝基-N-亚硝基胍(MNNG)诱导的GPL模型中的作用,并阐明其下游靶基因Kruppel样因子7(KLF7)在其中的作用。实验结果表明,在MNNG诱导的GES-1细胞模型中miR-520f-3p表达下调,miR-520f-3p的过表达逆转了MNNG对细胞迁移、侵袭及上皮-间质转化(EMT)相关蛋白表达的影响。同时,KLF7的过表达减弱了miR-520f-3p对GPL的作用。在小鼠GPL模型中,观察到MNNG通过KLF7/核因子κB(NFκB)途径引发小鼠胃组织的炎症和EMT过程,沉默KLF7可减轻MNNG诱导的胃上皮细胞损伤和胃萎缩症状。这些结果为理解GPL的发生发展提供了新的视角,针对miR-520f-3p和KLF7的新疗法的开发可能为胃癌的预防和治疗提供新思路。