Overexpression of USP39 predicts poor prognosis and promotes tumorigenesis of prostate cancer via promoting EGFR mRNA maturation and transcription elongation.

Castration resistance is a serious problem facing clinical treatment of prostate cancer (PCa). The underlying molecular mechanisms of acquired proliferation ability of tumor cells upon androgen deprivation are largely undetermined. In the present study, we identified that ubiquitin specific peptidase 39 (USP39) was significantly upregulated in PCa samples and cell lines. Elevated USP39 expression was positively correlated with Gleason score, predicted a poor outcome, and functioned as an independent risk factor for biochemical recurrence (BCR) especially in patients with a Gleason score ≤7. Our cell-based study showed that the expression level of USP39 was the highest in AR-negative PCa cell lines. Knockdown of USP39 in PCa cells inhibited cancer colony formation and tumor cell growth, and induced G2/M arrest and cell apoptosis. Microarray analysis suggested that knockdown of USP39 caused a reduced expression of EGFR. Silencing of USP39 inhibited the expression of EGFR 3'-end, and presented a remarkable block to the maturation of EGFR mRNA, suggesting that silencing of USP39 decreased the transcriptional elongation and maturation of EGFR mRNA. Oncomine datasets analysis showed that USP39 expression was positively correlated with EGFR level. The above findings suggest that USP39 plays a vital oncogenic role in the tumorigenesis of PCa and may prove to be a potential biomarker for predicting the prognosis of PCa patients.

Oxidized low-density lipoprotein, OXPAPC, corrects defects in maturation and cytokine secretion of peripheral blood dendritic cells from sepsis patients.

OBJECTIVE: To investigate the expression differences in maturation and cytokine production of dendritic cells (DCs) from sepsis patients and the effect of oxidized phospholipid 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (OXPAPC) on DCs phenotypes. METHODS: Peripheral blood mononuclear cells from 50 sepsis patients and 50 controls were cultured in the presence of GM-CSF, IL-4 and TNF-α to induce DCs maturation. DCs from sepsis patients were also treated with three different concentrations of OXPAPC. Cells were characterized with optical and electron microscopy, FACS analysis for CD1α, HLA-DR and CD86 on cell surface and ELISA analysis of IL-12p70 in the supernatant. RESULTS: DCs from sepsis patients had smaller cell bodies and nucleus and had almost no surface projection. DCs had similar CD1α expression in sepsis patients (86.37 ± 17.24) and controls (88.58 ± 10.05). HLA-DR expression was dramatically reduced in sepsis patients (2.74 ± 5.15) compared to controls (198.35 ± 12.04). Similarly, CD86 expression was also drastically lower in sepsis patients (14.72 ± 4.83) than controls (154.56 ± 11.56). Furthermore, OXPAPC treatment of DCs from sepsis patients increased cell surface projection, HLA-DR and CD86 surface expression and IL-12p70 secretion in a dose-dependent manner. With 40 µg/ml of OXPAPC, DCs of sepsis patients have similar phenotypes observed in healthy controls. CONCLUSION: DCs from sepsis patients are defective in maturation and cytokine secretion and these defects can be corrected by OXPAPC treatment.