Introduction: The immune checkpoints are closely associated with the development of various tumors. In this study, we aim to explore the interaction between immune checkpoint B7 homolog 4 (B7-H4) and androgen receptor (AR) and its specific mechanism in castrating resistance of prostate cancer.
Methods: LNCAP-AI cell model of human steroid-resistant prostate cancer was established by progressive androgen deprivation. Total RNA and total protein of the two kinds of cells were extracted, and the expressions of B7-H4 and AR were detected by RT-PCR and Western Blot. Then the direct binding sites of AR and B7-H4 promoters were detected by double luciferase reporting assay and chromatin immunoprecipitation assay. LNCap and LNCap-AI cell models with stable overexpression and knockout of B7-H4 were constructed to verify the regulatory relationship between B7-H4 and the JAK2/STAT3 signaling pathway, and then the influence of B7-H4 on the progression of castasis resistance of prostate cancer was detected by CCK-8 method, colony cloning-formation assay and flow cytometry. Finally, the above results were further verified by animal experiments.
Results: The expression of B7-H4 and AR in LNCap-AI cells was significantly higher than that in LNCap cells. Dual luciferase reporter assay showed that B7-H4 activation was regulated by androgen AR signaling pathway, and AR affected the proliferation, apoptosis, invasion and metastasis of prostate cancer cells by regulating the activity of B7-H4.
Conclusions: The expression of B7-H4 in prostate cancer is closely related to its progression, and AR affects the proliferation, apoptosis, invasion and metastasis of prostate cancer cells by regulating the activity of B7-H4, which may be a new target for the treatment of prostate cancer.
Source of Funding: This study was supported by the National Natural Science Foundation of China Project (No. 81874165)
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