Abstract
Expression of the immunoglobulin superfamily member CD155 was increased in a variety of human malignancies, but the role of CD155 in tumorigenesis and tumor development in cervical cancer has not been elucidated. In this study, immunohistochemistry and enzyme-linked immunosorbent assay analyses showed that CD155 expression gradually increases with the degree of cervical lesions. In vitro and in vivo, reducing the expression of CD155 inhibited cell proliferation, cell viability and tumor formation and arrested the cell cycle in G0/G1 phase. Antibody array-based profiling of protein phosphorylation revealed that CD155 knockdown can inhibited the AKT/mTOR/NF-κB pathway and activated autophagy and apoptosis; the opposite effects were observed upon CD155 has overexpression. We proved that there is an interaction between CD155 and AKT by immunoprecipitation. We further confirmed the mechanism between CD155 and AKT/mTOR/NF-κB through rescue experiments. AKT knockdown reversed the anti-apoptotic effects and activation of the AKT/mTOR/NF-κB pathway induced by CD155 overexpression. Our research demonstrated that CD155 can interact with AKT to form a complex, activates the AKT/mTOR/NF-κB pathway and inhibit autophagy and apoptosis. Thus, CD155 is a potential screening and therapeutic biomarker for cervical cancer.
Highlights
Cervical cancer is the fourth most common female malignancy in morbidity and mortality [1]
We evaluated the diagnostic significance of CD155 in cervical cancer and HSIL via receiver operating characteristic (ROC) analysis
Proteins related to the AKT/mTOR and NF-kB pathways showed the most obvious changes after CD155silencing (Figure 4A), and we focused on these pathways in our subsequent analyses Western blot analysis revealed that the LC3BII/LC3BI ratio and Beclin1 expression were increased in CD155- silenced CaSki and HeLa cells
Summary
Cervical cancer is the fourth most common female malignancy in morbidity and mortality [1]. There were more than 569,000 new cases of cervical cancer and 311,000 deaths in 2018 [1]. The main cause of cervical cancer is human papillomavirus (HPV) infection [2]. Not all women infected with HPV develop cervical cancer, which may be due to differences in epigenetic modifications [3]. The identification of new markers that can predict cervical cancer would aid diagnosis and potentially provide targets for treatment. Potential role of CD155 in the development of cervical cancer is unknown. Co-immunoprecipitation (Co-IP) assay and rescue assay confirmed that CD155 can interact with AKT to form CD155/AKT complex, and further promote the proliferation of cervical cancer cells and inhibit autophagy through AKT/mTOR and NF-kB pathways
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