<i>Porphyromonas gingivalis</i> Promotes the Proliferation and Migration of Esophageal Squamous Cell Carcinoma through the miR-194/GRHL3/PTEN/Akt Axis

Abstract

Recent studies have revealed that <i>Porphyromonas gingivalis</i> is closely related to the occurrence and progression of esophageal squamous cell carcinoma (ESCC). However, the underlying mechanism of <i>P. gingivalis</i> in ESCC has not been well elucidated. To explore the mechanism of <i>P. gingivalis</i> infection in ESCC, cellular proliferation, invasion, and migration models of KYSE-30 and KYSE-150 cells infected by <i>P. gingivalis</i> at a multiplicity of infection (MOI) of 10 were established. The results showed that <i>P. gingivalis</i> infection could drastically increase the proliferation, invasion, and migration ability of ESCC. Furthermore, the results of high-throughput sequencing showed that miR-194 was considerably upregulated in infected cells compared with control cells, which was further verified by qRT-PCR. The inhibition or overexpression of miR-194 had a significant effect on KYSE-30 and KYSE-150 cell migration and invasion. Additionally, the levels of GRHL3 and PTEN were decreased in <i>P. gingivalis</i>-infected esophageal cancer cells compared with uninfected esophageal cancer cells. Furthermore, dual-luciferase experiments confirmed that GRHL3 is a direct target of miR-194. In addition, the GRHL3-related pathway was investigated, and the levels of GRHL3 and PTEN were downregulated while the level of p-Akt was upregulated after <i>P. gingivalis</i> infection. Taken together, these findings indicated that <i>P. gingivalis</i> might promote ESCC proliferation and migration via the miR-194/GRHL3/PTEN/Akt signaling axis.