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  • Title: Protein kinase D3 regulates the expression of the immunosuppressive protein, PD‑L1, through STAT1/STAT3 signaling.
    Author: Cui B, Chen J, Luo M, Wang L, Chen H, Kang Y, Wang J, Zhou X, Feng Y, Zhang P.
    Journal: Int J Oncol; 2020 Apr; 56(4):909-920. PubMed ID: 32319563.
    Abstract:
    Oral squamous cell carcinoma (OSCC) is capable of constructing a favorable immune escape environment through interactions of cells with cells and of cells with the environment. Programmed death ligand‑1 (PD‑L1) is a well‑recognized inhibitor of anti‑tumor immunity that plays an important role in tumor immune escape. However, the molecular mechanisms regulating PD‑L1 expression are not yet fully understood. In this study, to investigate the role of protein kinase D3 (PKD3) in the regulation of PD‑L1 expression, the expression and correlation of PKD3 and PD‑L1 were first analyzed by the immunostaining of human OSCC tissue sections, cell experiments and TCGA gene expression databases. The expression levels of PKD3 and PD‑L1 were found to be significantly higher in OSCC cells than in normal tissues or cells. In addition, the expression levels of PKD3 and PD‑L1 were found to be significantly positively correlated. Subsequently, it was found that the levsel of PD‑L1 expression decreased following the silencing of PKD3 and that the ability of interferon (IFN)‑γ to induce PD‑L1 expression was also decreased in OSCC. The opposite phenomenon occurred following the overexpression of PKD3. It was also found that the phosphorylation of signal transducer and activator of transcription (STAT)1/STAT3 was reduced by the knockdown of PKD3 in OSCC. Moreover, the expression level of PD‑L1 was decreased after the use of siRNA to knockdown STAT1 or STAT3. On the whole, the findings of this study confirm that PKD3 regulates the expression of PD‑L1 induced by IFN‑γ by regulating the phosphorylation of STAT1/STAT3. These findings broaden the understanding of the biological function of PKD3, suggesting that PKD is a potential therapeutic target for OSCC.
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