Porphyromonas gingivalis-induced HuR upregulation suppresses SLC39A10-derived hsa_circ_0057552 in esophageal squamous cell carcinoma.

IF 2.7 4区医学 Q3 IMMUNOLOGY

Microbes and Infection Pub Date : 2025-07-21 DOI:10.1016/j.micinf.2025.105548

Rui Yang, Bianli Gu, Qi Jiang, Linlin Shi, Shuoxuan Li, Yaowu Lang, Yongtian Li, Zhixiang Zuo, Shegan Gao

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引用次数: 0

Abstract

Porphyromonas gingivalis (P. gingivalis) is one of the main risk factors of esophageal squamous cell carcinoma (ESCC). Circular RNAs (circRNAs) have been found to play a crucial role in many types of cancer. However, its functional involvement in P. gingivalis-infected ESCC remained understudied. In this study, we investigate that overexpression of hsa_circ_0057552 inhibited the proliferation and motility of ESCC cells in vitro and in vivo, whereas its silencing exerts the opposite effect. Hsa_circ_0057552 was found to be downregulated in P. gingivalis-infected ESCC tissues and cells, with the extent of downregulation correlating with both the dose and duration of P. gingivalis infection. Mechanistically, P. gingivalis infection significantly reduced the stability of hsa_circ_0057552 in ESCC cells, and Human Antigen R (HuR) was identified as a key regulator mediating this destabilization. The interaction between hsa_circ_0057552 and HuR was confirmed. Furthermore, hsa_circ_0057552 suppressed SLC39A10 mRNA expression by competitively inhibiting HuR binding to SLC39A10 transcripts. This study delineates a P. gingivalis-HuR-hsa_circ_0057552 axis that may modulate SLC39A10 availability through competitive RNA-protein interactions. This mechanistic framework suggests a dual therapeutic approach: microbial-targeted eradication of P. gingivalis combined with hsa_circ_0057552 restoration therapy to disrupt oncogenic signaling cascades.

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食管鳞状细胞癌中牙龈卟啉单胞菌诱导的HuR上调抑制slc39a10衍生的hsa_circ_0057552

牙龈卟啉单胞菌（P. gingivalis）是食管鳞状细胞癌的主要危险因素之一。环状rna （circRNAs）已被发现在许多类型的癌症中起着至关重要的作用。然而，其在牙龈假单胞菌感染ESCC中的功能参与仍未得到充分研究。在本研究中，我们研究了过表达has_circ_0057552在体外和体内抑制ESCC细胞的增殖和运动，而沉默has_circ_0057552则起到相反的作用。Hsa_circ_0057552在牙龈假单胞菌感染的ESCC组织和细胞中下调，下调程度与牙龈假单胞菌感染的剂量和持续时间相关。从机制上看，P. gingivalis感染显著降低了ESCC细胞中hsa_circ_0057552的稳定性，而Human Antigen R （HuR）被确定为介导这种不稳定性的关键调节因子。hsa_circ_0057552与HuR的相互作用得到证实。此外，hsa_circ_0057552通过竞争性抑制HuR与SLC39A10转录本的结合来抑制SLC39A10 mRNA的表达。本研究描述了P. gingivalis-HuR-hsa_circ_0057552轴可能通过竞争性rna -蛋白相互作用调节SLC39A10的可用性。这一机制框架提示了一种双重治疗方法：以微生物为目标的牙龈卟啉菌根除联合hsa_circ_0057552恢复治疗来破坏致癌信号级联反应。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Microbes and Infection 医学-病毒学

CiteScore

12.60

自引率

1.70%

发文量

审稿时长

40 days

期刊介绍： Microbes and Infection publishes 10 peer-reviewed issues per year in all fields of infection and immunity, covering the different levels of host-microbe interactions, and in particular: the molecular biology and cell biology of the crosstalk between hosts (human and model organisms) and microbes (viruses, bacteria, parasites and fungi), including molecular virulence and evasion mechanisms. the immune response to infection, including pathogenesis and host susceptibility. emerging human infectious diseases. systems immunology. molecular epidemiology/genetics of host pathogen interactions. microbiota and host "interactions". vaccine development, including novel strategies and adjuvants. Clinical studies, accounts of clinical trials and biomarker studies in infectious diseases are within the scope of the journal. Microbes and Infection publishes articles on human pathogens or pathogens of model systems. However, articles on other microbes can be published if they contribute to our understanding of basic mechanisms of host-pathogen interactions. Purely descriptive and preliminary studies are discouraged.