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

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.