Biochemical and Biophysical Research Communications, Vol.503, No.1, 228-234, 2018
HIF-1 alpha induces immune escape of prostate cancer by regulating NCR1/NKp46 signaling through miR-224
Background: Metastasis of prostate cancer (PCa) is largely affected by natural killer (NK) cells. This study aimed to clarify the mechanisms underlying tumor cells escaping from NK cells mediated by HIF-1 alpha. Methods: MiR-224 expression in lymphocytes and HIF-1 alpha protein level in NK cells were determined by qRT-PCR and western blot, respectively. The amount of NKp46(+) NK cells was detected with flow cytometry. The IFN-gamma level was examined by enzyme linked immunosorbent assay (ELISA). NK cells were tested for cytolytic activity with a Non-Radioactive Cytotoxicity Assay, and treated with oxygenglucose deprivation (OGD) for hypoxia simulation. Interaction between miR-224 and NCRI was evaluated with dual luciferase reporter assay. Results: MiR-224 was down-regulated in lymphocytes isolated from prostate cancer tissues (n = 10). Overexpression of miR-224 protected prostate cancer from NM cells. HIF-1 alpha increased miR-224 to inhibit the killing capability of NK cells on prostate cancer. MiR-224 controlled the expression of NCRI. Over-expression of miR-224 protected prostate cancer from NK cells through NCRI/NKp46 signaling. Suppression of HIF-1 alpha enhanced the cytotoxicity of NK cells on prostate cancer via miR-224/NCRI pathway. Conclusion: HIF-1 alpha inhibits NCRI/NKp46 pathway through up-regulating miR-224, which affects the killing capability of NK cells on prostate cancer, thus inducing immune escape of tumor cells. (C) 2018 Elsevier Inc. All rights reserved.