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Background <p><i>Salmonella typhimurium</i> (<i>S. typhimurium</i>) 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 <i>S. typhimurium</i> 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 <i>S. typhimurium</i> infection in colorectal cancer (CRC).</p> Results <p>Transcriptomic analysis revealed numerous cellular circRNAs that were significantly regulated by <i>S. typhimurium</i> 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.</p> Conclusion <p>The <i>S. typhimurium</i>-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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月4日

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

摘要

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.