Journal
ACS INFECTIOUS DISEASES
Volume 6, Issue 5, Pages 871-881Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsinfecdis.0c00007
Keywords
esophageal squamous cell carcinoma; Porphyromonas gingivalis; miR-194; grainy head-like 3
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Funding
- National Natural Science Foundation of China [81741147, 81972571]
- China Postdoctoral Science Foundation [2019M652533]
- Henan Scientific and Technological Research Projects [192102310189]
- Innovative Scientists and Technicians Troop Construction Projects of Henan Province [CXTD2017071]
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Recent studies have revealed that Porphyromonas gingivalis is closely related to the occurrence and progression of esophageal squamous cell carcinoma (ESCC). However, the underlying mechanism of P. gingivalis in ESCC has not been well elucidated. To explore the mechanism of P. gingivalis infection in ESCC, cellular proliferation, invasion, and migration models of KYSE-30 and KYSE-150 cells infected by P. gingivalis at a multiplicity of infection (MOI) of 10 were established. The results showed that P. gingivalis 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 P. gingivalis-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 P. gingivalis infection. Taken together, these findings indicated that P. gingivalis might promote ESCC proliferation and migration via the miR194/GRHL3/PTEN/Akt signaling axis.
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