USP54 is a potential therapeutic target in castration-resistant prostate cancer.

BACKGROUND: USP54, a ubiquitin-specific protease in the deubiquitinase (DUB) family, facilitates the malignant progression of several types of cancer. However, the role of USP54 in prostate cancer (PCa), especially castration-resistant prostate cancer (CRPC), remains unknown. METHODS: We established the CRPC LNCaP-AI cell line from the hormone-sensitive prostate cancer (HSPC) LNCaP cell line. RNA-Seq was utilized to explore DUB expression levels in LNCaP and LNCaP-AI. USP54 was knocked down, and its effects on cell growth were evaluated in vitro and in vivo. Bioinformatics analyses were conducted to explore signaling pathways affected by USP54 in PCa. Quantitative polymerase chain reaction was used to confirm key signaling pathways involved. RESULTS: USP54 was the most strongly upregulated DUB in LNCaP-AI cells compared with LNCaP cells. USP54 levels were higher in PCa than in normal tissues. USP54 silencing suppressed the proliferation of PCa cell lines, both in vitro and in vivo. USP54 expression was positively correlated with the androgen receptor (AR) signaling level in PCa samples, and USP54 knockdown inhibited AR signaling in PCa cells. CONCLUSIONS: USP54 was upregulated during HSPC progression to CRPC. USP54 depletion suppressed CRPC cell proliferation both in vitro and in vivo. USP54 may facilitate PCa progression by regulating AR signaling.

ANP32B inhibition suppresses the growth of prostate cancer cells by regulating c-Myc signaling.

ANP32B is a histone chaperone that interacts with various transcription factors that regulate cancer cell proliferation, immigration, and apoptosis. c-Myc, a well-known oncogenic protein, is a principal player in the initiation and progression of prostate cancer (PC). The means by which ANP32B and c-Myc act remain unknown. We downloaded clinical data from the GEO, TCGA, and other databases to explore ANP32B expression and its effects on the survival of PC and normal tissues. ANP32B-knockdown cell lines were used to evaluate how ANP32B affected cell proliferation in vitro and in vivo. Gene set enrichment analysis and RNAseq were employed to define how ANP32B regulated PC pathways. Immunohistochemical measures were used to detect the expression levels of relevant proteins in xenografts and PC tissues. ANP32B expression increased in PC tissues; ANP32B knockdown inhibited cell growth but this was rescued by c-Myc signaling. ANP32B is thus a PC oncogene and may serve as a valuable therapeutic target when seeking to treat PC.

Identification of molecular subtypes and a prognostic signature based on chromatin regulators related genes in prostate cancer.

The clinical and molecular phenotypes of prostate cancer (PCa) exhibit substantial heterogeneity, ranging from indolent to metastatic disease. In this study, we aimed to identify PCa subtypes and construct a gene signature that can predict the recurrence-free survival (RFS) of PCa patients based on chromatin regulators genes (CRGs). Strikingly, we identified two heterogeneous subtypes with distinct clinical and molecular characteristics. Furthermore, by performing differential analysis between the two CRGs subtypes, we successfully constructed a gene signature to predict PCa prognosis. The signature, comprising four genes (MXD3, SSTR1, AMH and PPFIA2), was utilized to classify PCa patients into two risk groups; the high-risk group was characterized by poor prognosis and more aggressive clinical features. Moreover, we investigated the immune profile, mutation landscape and molecular pathways in each of the groups. Additionally, drug-susceptibility testing was performed to explore sensitive drugs for high-risk patients. Furthermore, we found that MXD3 downregulation suppressed the proliferation of PCa cell lines in vitro. Overall, our results highlight the signature based on CRGs as a powerful tool for predicting RFS of PCa patients, as well as an indicator for personalized treatment of those patients.

[The Expression of Sphingosine-1-phosphate and Sphingosine-1-phosphate Receptor 1 in Mouse Model of Pulmonary Ischemia-Reperfusion Injury].

OBJECTIVE: To investigate the expressions of sphingosine 1-phosphate (S1P) and S1P G-protein-coupled receptor 1 (S1PR1) in pulmonary ischemia reperfusion injury (PIRI) tissues and explore their relationship. METHODS: The model of PIRI was established in vivo male C57BL/6 mice (n=8). The left pulmonary hilum was occluded for 30 min with a microvascular clamp through a left thoracotomy. Reperfusion began with removal of the clamp. Normal group (n=8) and sham group (n=8) were set as control. The hematoxylin and eosin (HE) staining of ultrastructural changes and wet-to-dry mass ratio in lung tissues were measured for judging the succeed model. The mRNA expressions of sphingosine kinase 1 (SphK1) and S1PR1 were determined by real-time PCR, and ELISA was used to detect the concentrations of S1P and S1PR1 in the lung tissues. RESULTS: The mRNA expressions of SphK1, S1PR1 and the concentrations of S1P and S1PR1 and wet-to-dry mass ratio of the lung tissues in ischemia-reperfusion mice were higher than those normal mice and sham operation mice (P<0.05). CONCLUSIONS: The increased expressions of S1P and S1PR1 in lung tissues after PIRI suggest that the S1P/S1PR1 signal pathway is involved in the pathophysiological process of PIRI, and may be a potential therapeutic target for it.

A ratiometric fluorescence probe for imaging sulfur dioxide derivatives in the mitochondria of living cells.

Although sulfur dioxide (SO2) plays an essential role in several physiological processes, monitoring of intracellular SO2 at subcellular levels remains challenging due to the lack of rapid and sensitive methods for its quantification in a 100% aqueous solution. Herein, a new hemicyanine dyes-based fluorescence probe, NBD-Id, was designed and synthesized for the detection of SO2 derivatives in pure aqueous solution and living cells. By virtue of a specific 1,4-addition reaction of SO32-HSO3- and the polymethine chain of hemicyanine, significant changes in the absorption and fluorescence emission spectra were observed in less than 20 seconds. The ratiometric fluorescence (F467/F593) detection of SO2 derivatives was then obtained with high sensitivity (detection limit 3.6 nM). It was noted that NBD-Id has a specific response towards SO2 derivatives without interference from other anions and biomolecules. Intracellular fluorescence imaging indicated that NBD-Id is cell membrane permeable and mainly distributed within the mitochondria. Therefore, ratiometric fluorescence imaging of SO2 derivatives in the mitochondria of MCF-7 cells was successfully demonstrated.

Identification of amino-acid residues in the V protein of peste des petits ruminants essential for interference and suppression of STAT-mediated interferon signaling.

Peste des petits ruminants virus (PPRV) causes a fatal disease in small ruminants. V protein of PPRV plays a pivotal role in interfering with host innate immunity by blocking IFNs signaling through interacting with STAT1 and STAT2. In the present study, the results demonstrated that PPRV V protein blocks IFN actions in a dose dependent manner and restrains the translocation of STAT1/2 proteins. We speculate that the translocation inhibition might be caused by the interfering of the downstream of STAT protein. Mutagenesis defines that Cys cluster and Trp motif of PPRV V protein are essential for STAT-mediated IFN signaling. These findings give a new sight for the further studies to understand the delicate mechanism of PPRV to escape the IFN signaling.

Magnesium hydroxide nanoparticles synthesized in water-in-oil microemulsions.

Well-dispersed magnesium hydroxide nanoplatelets were synthesized by a simple water-in-oil (w/o) microemulsion process, blowing gaseous ammonia (NH(3)) into microemulsion zones solubilized by magnesium chloride solution (MgCl(2)). Typical quaternary microemulsions of Triton X-100/cyclohexane/n-hexanol/water were used as space-confining microreactors for the nucleation, growth, and crystallization of magnesium hydroxide nanoparticles. The obtained magnesium hydroxide was characterized by field-emission scanning electron microscopy (FESEM), high-resolution transmission election microscopy (HRTEM), X-ray powder diffraction (XRD), laser light scattering, Fourier transform infrared spectroscopy (FT-IR), and thermogravimetric analysis-differential scanning calorimetry (TGA-DSC). The mole ratio of water to surfactant (omega(0)) played an important role in the sizes of micelles and nanoparticles, increasing with the increase of omega(0). The compatibility and dispersibility of nanoparticles obtained from reverse micelles were improved in the organic phase.