PLK4 initiates crosstalk between cell cycle, cell proliferation and macrophages infiltration in gliomas.

Abstract

Tumor immune microenvironment plays an important role in tumorigenesis and metastasis. Polo-like kinases 4 (PLK4) is a crucial regulatory factor in the process of cell cycle, and its abnormal regulation often leads to a variety of diseases including tumorigenesis. We have previously explored the function of PLK4 in sensitizing chemotherapy in glioma, but there are few studies on the correlation between PLK4 and tumor immune microenvironment. PLK4 was found to be highly expressed in various types of cancers, including glioma and closely related to histological and genetic features in public databases. Kaplan-Meier survival analysis and Cox regression analysis revealed that higher PLK4 expression is associated with poorer prognosis. GO and KEGG functional enrichment analysis showed that PLK4 expression level was significantly correlated with regulation of immune microenvironment, cell cycle and genomic instability. Immune infiltration analysis showed that high expression of PLK4 resulted in reduced infiltration of macrophages. M1 macrophage infiltration assays showed that PLK4 knockdown GBM cell lines promoted the recruitment of M1-type macrophages via altering expression of chemokines. And in intracranial tumor mouse models, PLK4 inhibition increased tumor-infiltrating M1 macrophages. In summary, our results demonstrated the correlation between high PLK4 expression level and malignant progression of gliomas, and the possible involvement of PLK4 in regulation of cell cycle, cell proliferation and macrophages infiltration in gliomas.