Porphyromonas gingivalis Infection
Promoted the Proliferation of Oral Squamous Cell Carcinoma Cells through
the miR-21/PDCD4/AP‑1 Negative Signaling Pathway
posted on 2019-06-06, 00:00authored byChunrong Chang, Hongyan Wang, Junchao Liu, Chunling Pan, Dongmei Zhang, Xin Li, Yaping Pan
Recent epidemiological
studies have revealed that Porphyromonas
gingivalis, a major pathogen in periodontal disease, is associated
with the development of oral squamous cell carcinoma (OSCC). However,
the underlying mechanisms induced by P. gingivalis have not been well-defined. We aimed to determine the role of P. gingivalis in OSCC proliferation and the relevant
molecular mechanisms. A cellular proliferation model of OSCC Tca8113
cells infected by P. gingivalis at a multiplicity
of infection (MOI) of 50 was established. Cell proliferation was drastically
increased in the infected cells compared with the control cells, while
the proportion of cells in S phase was increased and the proportion
of cells in G1 phase was decreased in the infected cells compared
with the control cells. Additionally, the levels of activator protein
1 (AP-1; c-Jun and c-Fos) and its target gene cyclin D1 were increased
in P. gingivalis-infected Tca8113 cells compared
with control cells. miR-21 expression was elevated when programmed
cell death 4 (PDCD4) expression was downregulated. Cyclin D1 expression
was regulated by miR-21, PDCD4, and AP-1. The disruption of the pathway
by silencing c-Jun, blocking miR-21 expression, or overexpressing
PDCD4 led to decreased cyclin D1 expression and inhibited cell proliferation. P. gingivalis DNA levels were positively correlated
with miR-21 and c-Jun expression and negatively correlated with PDCD4
expression in clinical OSCC samples. Our findings indicated that P. gingivalis might promote OSCC proliferation by regulating
cyclin D1 expression via the miR-21/PDCD4/AP-1 negative feedback signaling
pathway.