BOP1 Promotes Prostate Cancer through the DUSP6/MAPK Pathway.

BACKGROUND: Nucleolar prominence is a biomarker of prostate cancer (CaP), and the nucleolar protein block of proliferation 1 (BOP1) participates in the development of CaP, which has great significance for CaP therapy. Thus, this study explored the mechanism of BOP1 in CaP development. METHODS: BOP1 expression levels in the tumor tissues of CaP patients and in PC3 tumor cells were determined. The viability, apoptosis rate of PC3 cells, and apoptosis-related proteins levels were determined to explore the effect of BOP1 on tumor-cell growth in vitro. BOP1 function in the metastasis of PC3 cells was further assessed by Transwell experiment. We also studied the influence of BOP1 on the expression of mitogen-activated protein kinase (MAPK) pathway-related proteins and investigated the regulatory effect of BOP1 on dual-specificity phosphatase 6 (DUSP6). RESULTS: BOP1 expression was upregulated in the tumor tissues and PC3 cells of CaP patients. BOP1 knockout reduced the activity of PC3 cells and induced apoptosis, significantly inhibiting the metastasis of PC3 cells. DUSP6 was overexpressed in tumor tissues and PC3 cells. BOP1 knockout inhibited DUSP6 expression and the MAPK pathway. DUSP6 overexpression reversed the inhibition of BOP1 siRNA (si-BOP1) on PC3 cells and the activated MAPK signaling pathway. CONCLUSIONS: This finding demonstrated that BOP1 promoted CaP progression by regulating the DUSP6/MAPK pathway.

BOP1 Promotes Prostate Cancer through the DUSP6/MAPK Pathway

Background: Nucleolar prominence is a biomarker of prostate cancer (CaP), and the nucleolar protein block of proliferation 1 (BOP1) participates in the development of CaP, which has great significance for CaP therapy. Thus, this study explored the mechanism of BOP1 in CaP development. Methods: BOP1 expression levels in the tumor tissues of CaP patients and in PC3 tumor cells were determined. The viability, apoptosis rate of PC3 cells, and apoptosis-related proteins levels were determined to explore the effect of BOP1 on tumor-cell growth in vitro. BOP1 function in the metastasis of PC3 cells was further assessed by Transwell experiment. We also studied the influence of BOP1 on the expression of mitogen-activated protein kinase (MAPK) pathway-related proteins and investigated the regulatory effect of BOP1 on dual-specificity phosphatase 6 (DUSP6). Results: BOP1 expression was upregulated in the tumor tissues and PC3 cells of CaP patients. BOP1 knockout reduced the activity of PC3 cells and induced apoptosis, significantly inhibiting the metastasis of PC3 cells. DUSP6 was overexpressed in tumor tissues and PC3 cells. BOP1 knockout inhibited DUSP6 expression and the MAPK pathway. DUSP6 overexpression reversed the inhibition of BOP1 siRNA (si-BOP1) on PC3 cells and the activated MAPK signaling pathway. Conclusions: This finding demonstrated that BOP1 promoted CaP progression by regulating the DUSP6/MAPK pathway (AU)

Comparison of the effect of bone marrow cells infusion through the portal vein and inferior vena cava combined with short-term rapamycin on allogeneic islet grafts in diabetic rats.

AIMS/INTRODUCTION: The study aimed to compare the impact of allogeneic bone marrow cells (BMCs) infusion through the inferior vena cava (IVC) and portal vein (PV) combined with rapamycin on allogeneic islet grafts in diabetic rats. MATERIALS AND METHODS: Recipient diabetic Wistar rats were infused with islets from Sprague-Dawley rats through the PV. PKH26-labeled BMCs of Sprague-Dawley rats were infused to recipients through the PV or IVC, followed by administration of rapamycin for 4 days. Blood glucose level was measured to evaluate the survival time of the islets. Lymphocytes separated from blood, BMCs, thymus, liver, spleen and lymph node were analyzed by flow cytometry. The peripheral blood smear, BMCs smear and frozen sections of tissues were observed by a fluorescence microscope. RESULTS: The survival time of the islets was significantly prolonged by the BMCs infusion combined with rapamycin. The rats receiving BMCs infusion through the PV induced a significantly longer survival time of the islets, and increased mixed chimeras of allogeneic BMCs in the thymus, liver, spleen and lymph node compared with the rats receiving BMCs infusion through the IVC. The amount of the mixed chimeras on day 14 was lower than that on day 7 after islet transplantation. Furthermore, PV transplantation had significantly more mixed chimera than IVC transplantation in all analyzed organs or tissues. CONCLUSIONS: BMCs infusion combined with rapamycin prolongs the islets survival and induces mixed chimeras of BMCs. PV infusion of BMCs might be a more effective strategy than IVC infusion of BMCs.

Vitamin D-binding protein in cerebrospinal fluid is associated with multiple sclerosis progression.

Multiple sclerosis is a neurological disorder that presents with symptoms including inflammation, neurodegeneration, and demyelination of the central nervous system (CNS). Secondary progressive multiple sclerosis (SPMS) manifests with serious physical disability. To quantitatively analyze differential protein expression in patients with SPMS, we performed two-dimensional fluorescence difference in-gel electrophoresis, followed by mass spectrometry on the cerebrospinal fluid of these patients and patients with other neurological diseases. Vitamin D-binding protein (DBP), gelsolin, albumin, etc. showed more than a 1.5-fold difference between the two groups. Based on these results, an experimental allergic encephalomyelitis (EAE) model of multiple sclerosis in Lewis rats was used to investigate DBP's role in the disease. Protein levels, mRNA transcripts, and ligands of DBP in different regions of the CNS were evaluated under various vitamin D intake levels. Here, DBP levels increased in the experimental rat groups compared to the control groups regardless of vitamin D intake. Moreover, DBP mRNA levels varied in different parts of the CNS including spinal cords in the experimental groups. The observed differences between DBP protein and mRNA levels in the experimental groups' spinal cords could be derived from the disruption of the blood-brain barrier. Furthermore, an interaction between DBP and actin was confirmed using coimmunoprecipitation and western blot. These results indicate a role for DBP in the actin scavenge system. Moreover, in the experimental group that received oral vitamin D3 supplement, we observed both delayed onset and diminished severity of the disease. When DBP was upregulated, however, the benefits from the vitamin D3 supplements were lost. Thus, we inferred that high levels of DBP were adverse to recovery. In conclusion, here we observed upregulated DBP in the cerebrospinal fluid could serve as a specific diagnostic biomarker for the progression of multiple sclerosis. Next, we demonstrate the vital function of increased levels of free vitamin D metabolites for multiple sclerosis treatment. Finally, vitamin D supplements may be particularly beneficial for SPMS patients.