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

Abstract

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 miR-194/GRHL3/PTEN/Akt signaling axis.

Exosomal microRNA‐139‐5p from mesenchymal stem cells accelerates trophoblast cell invasion and migration by motivation of the ERK/MMP‐2 pathway via downregulation of protein tyrosine phosphatase

“…Another critical conclusion was that exosomal miR‐139‐5p could downregulate PTEN and trigger the ERK/MMP‐2 pathway. It was stated that PTEN was strongly connected to various tumors, including breast, endometrial and esophageal squamous cell carcinomas 31–33 . More specifically, PTEN was also found to play a part in trophoblast cell proliferation and PE development regulated by long noncoding RNA T cell leukemia/lymphoma 6 34 .…”

“…It was stated that PTEN was strongly connected to various tumors, including breast, endometrial and esophageal squamous cell carcinomas. [31][32][33] More specifically, PTEN was also found to play a part in trophoblast cell proliferation and PE development regulated by long noncoding RNA T cell leukemia/lymphoma 6. 34 Moreover, strengthened PTEN in HTR-8/SVneo cells displayed partial degeneration of the improved cell infiltration prompted by miR-21.…”

Porphyromonas gingivalis and Its Systemic Impact: Current Status

“…Further, Yuan et al highlighted the ability of P. gingivalis to evade immune surveillance, and they determined that the blockade of immune-checkpoint B7-H4 and lysine demethylase 5b in ESCC conferred resistance against P. gingivalis infection and tumor challenge, proposing them as potential therapeutic targets for controlling P. gingivalis infection and its associated neoplasia [ 86 ]. Furthermore, P. gingivalis can enhance ESCC cell proliferation and metastasis by triggering the NF-κB signaling pathway [ 87 ] or via the miR-194/GRHL3/PTEN/Akt axis [ 88 ].…”

Frequencies of Porphyromonas gingivalis Detection in Oral-Digestive Tract Tumors

“…Although P. gingivalis has been proven to invade gingival epithelial cells [ 12 ], studies on its presence in the epithelium of different sites of the digestive tract are scarce. Previously, our group found that P. gingivalis detection may be a high-risk factor for esophageal squamous cell carcinoma (ESCC), and was correlated with the development of esophageal cancer [ 13 – 17 ]. These reports indicate that chronic bacterial infection with P. gingivalis is an important etiological factor of tumor development and progression.…”