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

牙龈卟啉单胞菌 PTEN公司 蛋白激酶B 癌症研究 下调和上调 细胞迁移 感染的多重性 PI3K/AKT/mTOR通路 细胞 化学 信号转导 细胞生长 生物 医学 内科学 细胞生物学 基因 生物化学 牙周炎
作者
Gaofeng Liang,Haojie Wang,Hao Shi,Mengxi Zhu,Junling An,Yijun Qi,Jingxia Du,Yan Li,Shegan Gao
出处
期刊:ACS Infectious Diseases [American Chemical Society]
卷期号:6 (5): 871-881 被引量:38
标识
DOI:10.1021/acsinfecdis.0c00007
摘要

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.
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