| Popis: |
Background High mobility group box 1 protein (HMGB1) is known to be associated with progression, metastasis, and poor prognosis of several solid tumors, but the role of HMGB1 in prostate cancer (PCa) has remained unclear. Thus, we aimed to evaluate the clinical significance and the biological mechanism of HMGB1 in PCa. Methods To explore the clinical significance of HMGB1 in PCa, we performed IHC analyses using paraffin-embedded tissues from patients with low-, intermediate-, and high-risk PCa and from patients with BPH. Biological role and mechanism of HMGB1 in PCa were analyzed using cell viability, cell cycle, Western blot analyses, proteome profiler antibody array, and co-immunoprecipitation assay. Results We showed that increases in the expression of HMGB1 correlated with an increased risk of aggressive PCa, and high expression of HMGB1 was associated with poor biochemical recurrence-free survival in a Korean cohort. The inhibition of HMGB1 expression significantly reduced cell proliferation and increased cell cycle arrest in the sub-G0 phase. It also inhibited the invasive capacity of PCa cells in vitro. The above processes were mediated through the binding with TNFR1, leading to tumor progression by activation of the NF-κB signaling pathway. Conclusions We identified that HMGB1 is a critical factor in the development and progression of PCa by regulating the HMGB1/TNFR1/NF-κB signaling pathway. HMGB1/TNFR1 could serve as a novel therapeutic target for improving PCa therapy. |
