鼠伤寒沙门菌通过CeRNA机制下调circHIPK2表达，抑制细胞迁移和肿瘤发生。

IF 4 3区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Gut Pathogens Pub Date : 2025-10-04 DOI:10.1186/s13099-025-00759-4

Fei Wang, Xiaoting Luan, Huihui Ma, Xiaoyi Wang, Minchi Chen, Yuyu Xu

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引用次数: 0

摘要

背景：鼠伤寒沙门氏菌（S. typhimurium）是引起胃肠道疾病的典型肠道病原菌之一。环状RNA （circRNA）是一种共价的闭环RNA分子，缺乏3‘和5’端，在人类疾病的发病和进展中起着至关重要的作用。然而，在肿瘤发生和发展过程中，鼠伤寒沙门氏菌感染是否能调节宿主circRNAs的表达尚不清楚。本研究旨在探讨鼠伤寒沙门氏菌感染结肠直肠癌（CRC）中环状rna表达改变的治疗潜力和潜在机制。结果：转录组学分析显示，在结直肠癌细胞系HCT116中，鼠伤寒沙门氏菌显著调节了许多细胞环状rna。值得注意的是，其中circHIPK2表现出最明显的下调。敲低circHIPK2可抑制SL1344诱导的细胞运动、肿瘤生长和上皮细胞细胞因子如IL8、IL6和GM-CSF的表达。通过RNA分子结合实验证实circHIPK2与miR-124-3p之间存在相互作用。此外，过表达的miR-124-3p破坏了circHIPK2诱导的细胞运动。结论：鼠伤寒沙门氏菌调控的circHIPK2/miR-124-3p轴在结直肠癌发病中起关键作用，有望成为治疗结肠炎相关结直肠癌的分子治疗靶点。

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Salmonella typhimurium downregulates circHIPK2 expression via CeRNA mechanism to inhibit cell migration and tumorigenesis.

Background: Salmonella typhimurium (S. typhimurium) is one of the typical intestinal pathogens leading to gastrointestinal diseases. Circular RNA (circRNA) is a covalently closed-loop RNA molecule that lacks 3' and 5' ends, and it plays a crucial role in the pathogenesis and progression of human diseases. However, whether host circRNAs expression could be regulated by S. typhimurium infection during tumorigenesis and development is still not clear. This study aim is to explore the therapeutic potential and underlying mechanisms of altered circular RNAs expression in S. typhimurium infection in colorectal cancer (CRC).

Results: Transcriptomic analysis revealed numerous cellular circRNAs that were significantly regulated by S. typhimurium in the colorectal cancer cell line HCT116. Notably, circHIPK2 exhibited the most pronounced downregulation among them. Knockdown of circHIPK2 inhibited cell motility, tumor growth and epithelial cell cytokine expression like IL8, IL6 and GM-CSF induced by SL1344. The interaction between circHIPK2 with miR-124-3p was confirmed through RNA molecular binding experiment. Furthermore, overexpressed miR-124-3p abrogated cell motility induced by circHIPK2.

Conclusion: The S. typhimurium-regulated circHIPK2/miR-124-3p axis is pivotal in CRC pathogenesis and holds promise as a molecular therapeutic target for treating colitis-associated colorectal cancer.

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来源期刊

Gut Pathogens GASTROENTEROLOGY & HEPATOLOGY-MICROBIOLOGY

CiteScore

7.70

自引率

2.40%

发文量

期刊介绍： Gut Pathogens is a fast publishing, inclusive and prominent international journal which recognizes the need for a publishing platform uniquely tailored to reflect the full breadth of research in the biology and medicine of pathogens, commensals and functional microbiota of the gut. The journal publishes basic, clinical and cutting-edge research on all aspects of the above mentioned organisms including probiotic bacteria and yeasts and their products. The scope also covers the related ecology, molecular genetics, physiology and epidemiology of these microbes. The journal actively invites timely reports on the novel aspects of genomics, metagenomics, microbiota profiling and systems biology. Gut Pathogens will also consider, at the discretion of the editors, descriptive studies identifying a new genome sequence of a gut microbe or a series of related microbes (such as those obtained from new hosts, niches, settings, outbreaks and epidemics) and those obtained from single or multiple hosts at one or different time points (chronological evolution).