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1.
Artigo em Inglês | MEDLINE | ID: mdl-31584750

RESUMO

Electrochemical sensors are essential for point-of-care testing (POCT) and wearable sensing devices. Establishing an efficient electron transfer route between redox enzymes and electrodes is key for converting enzyme-catalyzed reactions into electrochemical signals, and for the development of robust, sensitive, and selective biosensors. We demonstrate that the site-specific incorporation of a novel synthetic amino acid (2-amino-3-(4-mercaptophenyl)propanoic acid) into redox enzymes, followed by an S-click reaction to wire the enzyme to the electrode, facilitates electron transfer. The fabricated biosensor demonstrated real-time and selective monitoring of tryptophan (Trp) in blood and sweat samples, with a linear range of 0.02-0.8 mm. Further developments along this route may result in dramatic expansion of portable electrochemical sensors for diverse health-determination molecules.

2.
J Med Chem ; 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31580660

RESUMO

Indoleamine 2,3-dioxygenase 1 (IDO1), which catalyzes the initial and rate-limiting step of the kynurenine pathway of tryptophan catabolism, has emerged as a key target in cancer immunotherapy because of its role in enabling cancers to evade the immune system. Tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase 2 (IDO2) catalyze the same reaction and play a potential role in cancer immunotherapy. Starting from our previously discovered tryptanthrin IDO1 inhibitor scaffold, we synthesized novel N-benzyl/aryl substituted tryptanthrin derivatives and evaluated their inhibitory efficacy on IDO1, TDO, and IDO2. Most compounds showed similar high inhibitory activities on both IDO1 and TDO, which were significantly superior over that of IDO2 with magnitude difference. We showed that N-benzyl/aryl substituted tryptanthrin directly interacted with IDO1, TDO, and IDO2, significantly augmented the proliferation of T cells in vitro, blocked the kynurenine pathway, and suppressed tumor growth when administered to LLC and H22 tumor-bearing mice.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31589397

RESUMO

We synthesized three conjugated polycarbazole porous organic frameworks named o-Cz-POF, m-Cz-POF and p-Cz-POF for hydrocarbon fuels adsorptive desulfurization. The carbazole building blocks possessed ortho, meta, and para steric configuration, which resulting in POFs exhibited adjustable specific surface area and pore structure. Adsorption kinetics experiments and DFT calculations were carried out to understand the competitive adsorption of 3-methylthiophene and octane in the Cz-POF. The instantaneous adsorption rate and adsorption energy calculation analyses gave a convincing demonstration on preferential selective adsorption of 3-methylthiophene in Cz-POFs. Furthermore, the fixed-bed breakthrough experiment demonstrated that the Cz-POFs can selectively adsorb 3-methylthiophene efficiently and hydrocarbon fuel with sulfide content close to 0 ppm was obtained. The features of high stability and high desulfurization efficiency of Cz-POFs make them hold the promise as a new type of porous adsorbents for the ultra-deep adsorption desulfurization.

4.
Microb Cell Fact ; 18(1): 162, 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31581942

RESUMO

BACKGROUND: Efficient and convenient genome-editing toolkits can expedite genomic research and strain improvement for desirable phenotypes. Zymomonas mobilis is a highly efficient ethanol-producing bacterium with a small genome size and desirable industrial characteristics, which makes it a promising chassis for biorefinery and synthetic biology studies. While classical techniques for genetic manipulation are available for Z. mobilis, efficient genetic engineering toolkits enabling rapidly systematic and high-throughput genome editing in Z. mobilis are still lacking. RESULTS: Using Cas12a (Cpf1) from Francisella novicida, a recombinant strain with inducible cas12a expression for genome editing was constructed in Z. mobilis ZM4, which can be used to mediate RNA-guided DNA cleavage at targeted genomic loci. gRNAs were then designed targeting the replicons of native plasmids of ZM4 with about 100% curing efficiency for three native plasmids. In addition, CRISPR-Cas12a recombineering was used to promote gene deletion and insertion in one step efficiently and precisely with efficiency up to 90%. Combined with single-stranded DNA (ssDNA), CRISPR-Cas12a system was also applied to introduce minor nucleotide modification precisely into the genome with high fidelity. Furthermore, the CRISPR-Cas12a system was employed to introduce a heterologous lactate dehydrogenase into Z. mobilis with a recombinant lactate-producing strain constructed. CONCLUSIONS: This study applied CRISPR-Cas12a in Z. mobilis and established a genome editing tool for efficient and convenient genome engineering in Z. mobilis including plasmid curing, gene deletion and insertion, as well as nucleotide substitution, which can also be employed for metabolic engineering to help divert the carbon flux from ethanol production to other products such as lactate demonstrated in this work. The CRISPR-Cas12a system established in this study thus provides a versatile and powerful genome-editing tool in Z. mobilis for functional genomic research, strain improvement, as well as synthetic microbial chassis development for economic biochemical production.


Assuntos
Edição de Genes/métodos , Genoma Bacteriano , Zymomonas/genética , Sistemas CRISPR-Cas , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Endonucleases/metabolismo , Francisella/enzimologia , Plasmídeos/genética , Plasmídeos/metabolismo , RNA Guia/genética , RNA Guia/metabolismo , Zymomonas/metabolismo
5.
Artigo em Inglês | MEDLINE | ID: mdl-31505783

RESUMO

In China, family doctor services originated in 2009. After two years, the Chinese government proposed the establishment of a family doctor contract system suitable for China's national conditions. Then, in 2016, a multi-department jointly issued an important document, which further clarified the development goals of family doctor contract services in the next five years. Zhejiang Province has been exploring responsible doctor contract services since 2012, which was promoted throughout the province in 2015. OBJECTIVES: The aim of this study was to investigate the residents' awareness of Zhejiang Province, China, of family doctor contract services, the status of signing such a contract, and the demand for service items in the contracted service package. Further, we sought to explore the relevant influential factors in order to provide a reference and evidence-based recommendations for the further development of family doctor contract services. DESIGN: We enrolled 3960 residents from nine counties in Zhejiang Province using a multistage stratified random sampling method. A survey using a self-designed questionnaire was used to collect the demographic data, residents' awareness of family doctor contract services, the status of contracting, and demand for different items from October to December 2017. Data were analyzed by SPSS 21.0. RESULTS: In total, 3871 residents returned valid questionnaires, with a response rate of 97.75%. The awareness rate of residents of family doctor contract services was 71.58% (2771/3871). Age, education level, and chronic medical history status were the influencing factors affecting residents' awareness. The contracted rate was 50.43% (1952/3871). Age, education level, personal monthly income, chronic disease history, and awareness of family doctor contract services were the influencing factors. Residents who have a contract with family doctors have a higher demand for family doctor contract services, and different residents have different needs for the project because of their physical condition, education level, marital status, household registration, and personal monthly income level. The top three needs of the residents for contracted services were health consultation (84.64%), regular physical examination (81.71%), and increasing the proportion of medical insurance reimbursements (80.06%). CONCLUSIONS: The awareness rate of family doctor contract services and the contracting rate are unsatisfactory among residents of Zhejiang Province. It is suggested that the government should more heavily publicize family doctor contract services, expand the coverage, introduce personalized contract schemes to meet the needs of different groups, and promote the rapid development of family doctor contract services in Zhejiang Province.

6.
Bioresour Technol ; 293: 122006, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31476564

RESUMO

The rapid growth of nitrite-oxidizing bacteria (NOB) in reactor prevents the application of anaerobic ammonium oxidation (anammox) technology to main-stream wastewater treatment. How to eliminate NOB and reserve anaerobic ammonium oxidation bacteria (AnAOB) simultaneously becomes the biggest challenge. In this study two coupled biological aeration filters (BAFs) were built up to treat domestic sewage. In BAF1 nitrogen removal concentration was 21.4 mg/L via heterotrophic denitrification pathway. Backwash was conducted to BAF2 to improve nitrogen removal performance. After backwash Nitrospira proportion declined from 10.8% to 2.1%, while Candidatus Kuenenia percentage increased from 5.6% to 10.2%. Nitrogen removal concentration improved from 8.6 mg/L to 22.8 mg/L via anammox pathway in BAF2, and total nitrogen removal concentration reached to 44.2 mg/L in two coupled BAFs during aeration process. These findings could provide a new strategy for the application of anammox technology to main-stream wastewater treatment.


Assuntos
Microbiota , Nitrogênio , Reatores Biológicos , Desnitrificação , Esgotos
7.
Emerg Infect Dis ; 25(10): 1861-1867, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31538558

RESUMO

Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is a public health concern worldwide, but comprehensive analysis of risk factors for CRPA remains limited in China. We conducted a retrospective observational study of carbapenem resistance in 71,880 P. aeruginosa isolates collected in Zhejiang Province during 2015-2017. We analyzed risk factors for CRPA, including the type of clinical specimen; the year, season, and region in which it was collected; patient information, including age, whether they were an outpatient or inpatient, and whether inpatients were in the intensive care unit or general ward; and the level of hospital submitting isolates. We found CRPA was more prevalent among isolates from patients >60 years of age and in inpatients, especially in intensive care units. In addition, specimen types and seasons in which they were collected were associated with higher rates of CRPA. Our findings can help hospitals reduce the spread of P. aeruginosa and optimize antimicrobial drug use.

8.
J Chem Inf Model ; 2019 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-31487462

RESUMO

ß-N-Acetylhexosaminidases have emerged as promising targets for drug and pesticide discovery due to their critical physiological functions in various cellular processes. In particular, human O-GlcNAcase (hOGA) from the glycoside hydrolase family 84 (GH84) has gained significant attention. This enzyme was found to be linked to various diseases such as diabetes, cancer, and Alzheimer's disease (AD). In this study, to develop novel hOGA inhibitors with suitable pharmaceutical properties, virtual screening of the Drugbank database was performed using a docking-based approach targeting hOGA. Chlorhexidine (4, Ki = 4.0 µM) was identified as a potent hOGA inhibitor with excellent selectivity (Ki > 200 µM against human ß-N-acetylhexosaminidase B) and subjected to structural modifications and SAR studies. Furthermore, molecular dynamics simulations as well as binding free energy and free energy decomposition calculations were carried out to investigate the basis for the efficiency of potent inhibitors against hOGA. This present work revealed the new application of the disinfectant chlorhexidine and provided useful information for the future design of hOGA inhibitors.

10.
Science ; 365(6457): 1017-1020, 2019 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-31488686

RESUMO

Spectrometers with ever-smaller footprints are sought after for a wide range of applications in which minimized size and weight are paramount, including emerging in situ characterization techniques. We report on an ultracompact microspectrometer design based on a single compositionally engineered nanowire. This platform is independent of the complex optical components or cavities that tend to constrain further miniaturization of current systems. We show that incident spectra can be computationally reconstructed from the different spectral response functions and measured photocurrents along the length of the nanowire. Our devices are capable of accurate, visible-range monochromatic and broadband light reconstruction, as well as spectral imaging from centimeter-scale focal planes down to lensless, single-cell-scale in situ mapping.

11.
FEBS J ; 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31482685

RESUMO

Non-small cell lung cancer (NSCLC) is the main type of lung cancer, with a low 5-year survival rate because of the absence of effective clinical biomarkers for early diagnosis. Based on the immunosurveillance theory, we proposed that changes in the immune system are more pronounced than tumour-associated antigens during the early stage of cancer. Therefore, a new strategy was designed to screen early diagnostic biomarkers from peripheral leukocytes in early-stage NSCLCs with transcriptome sequencing. A total of 358 immune-related differentially expressed genes were identified between early-NSCLC patients and healthy individuals. Orosomucoid-1 (ORM1, a acute phase protein), the total ORM and chitotriosidase-1 (involved in degradation of chitobiose) were selected for further verification in 210 serum samples by western blotting, ELISA and nephelometry immunoassay (based on immuno-scatter turbidmetry). Receiver operating characteristic curve analysis show that ORM1 and total ORM have excellent diagnostic efficacies, with area under the curve of 0.862 and 0.920, respectively, which significantly distinguished very early-NSCLC (IA) from healthy samples. Flow cytometry results showed that CD15+ neutrophils made up 73% of ORM1+ peripheral leukocytes. In mouse lung cancer model, serum ORM1, but not liver ORM1, changed significantly in the early stage of NSCLC. ORM1 expression in peripheral leukocytes was regulated by TGF-ß and mediated by the TGF-ß/Smad signalling pathway. Our results indicated that combined ORM and TGF-ß could be a promising clinical biomarker in the diagnosis of early NSCLC.

12.
Theranostics ; 9(21): 6063-6079, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31534537

RESUMO

Background: The reciprocal repressive loop between ZEB1 and miRNAs has been extensively reported to play an important role in tumor progression and metastasis of various human tumor types. The aim of this study was to elucidate the role and the underlying mechanism of the double-negative feedback loop between ZEB1and miR-33a-5p in bone metastasis of prostate cancer (PCa). Methods: miR-33a-5p expression was examined in 40 bone metastatic and 165 non-bone metastatic PCa tissues by real-time PCR. Statistical analysis was performed to evaluate the clinical correlation between miR-33a-5p expression and clinicopathological characteristics, and overall and bone metastasis-free survival in PCa patients. The biological roles of miR-33a-5p in bone metastasis of PCa were investigated both by EMT and the Transwell assay in vitro, and by a mouse model of left cardiac ventricle inoculation in vivo. siRNA library, real-time PCR and chromatin immunoprecipitation (ChIP) were used to identify the underlying mechanism responsible for the decreased expression of miR-33a-5p in PCa. Bioinformatics analysis, Western blotting and luciferase reporter analysis were employed to examine the relationship between miR-33a-5p and its potential targets. Clinical correlation of miR-33a-5p with its targets was examined in human PCa tissues and primary PCa cells. Results: miR-33a-5p expression was downregulated in PCa tissues with bone metastasis and bone-derived cells, and low expression of miR-33a-5p strongly and positively correlated with advanced clinicopathological characteristics, and shorter overall and bone metastasis-free survival in PCa patients. Upregulating miR-33a-5p inhibited, while silencing miR-33a-5p promoted EMT, invasion and migration of PCa cells. Importantly, upregulating miR-33a-5p significantly repressed bone metastasis of PC-3 cells in vivo. Our results further revealed that recurrent ZEB1 upregulation induced by copy number gains transcriptionally inhibited miR-33a-5p expression, contributing to the reduced expression of miR-33a-5p in bone metastatic PCa tissues. In turn, miR-33a-5p formed a double negative feedback loop with ZEB1 in target-independent manner, which was dependent on TGF-ß signaling. Finally, the clinical negative correlations of miR-33a-5p with ZEB1 expression and TGF-ß signaling activity were demonstrated in PCa tissues and primary PCa cells. Conclusion: Our findings elucidated that copy number gains of ZEB1-triggered a TGF-ß signaling-dependent miR-33a-5p-mediated negative feedback loop was highly relevant to the bone metastasis of PCa.

13.
Int J Mol Med ; 2019 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-31545482

RESUMO

There is now substantial evidence that myocardial ischemia­reperfusion (IR) injury affects the spinal cord and brain, and that interactions may exist between these two systems. In the present study, the spinal cord proteomes were systematically analyzed after myocardial IR injury, in an attempt to identify the proteins involved in the processes. The myocardial IR injury rat model was first established by cross clamping the left anterior descending coronary artery for 30­min ischemia, followed by reperfusion for 2 h, which resulted in a significant histopathological and functional myocardial injury. Then using the stable isotope dimethyl labeling quantitative proteomics strategy, a total of 2,362 shared proteins with a good distribution and correlation were successfully quantified. Among these proteins, 33 were identified which were upregulated and 57 were downregulated in the spinal cord after myocardial IR injury, which were involved in various biological processes, molecular function and cellular components. Based on these proteins, the spinal cord protein interaction network regulated by IR injury, including apoptosis, microtubule dynamics, stress­activated signaling and cellular metabolism was established. These heart­spinal cord interactions help explain the apparent randomness of cardiac events and provide new insights into future novel therapies to prevent myocardial I/R injury.

14.
Magn Reson Med ; 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31502708

RESUMO

PURPOSE: To present a 3T brain imaging study using a conformal prototype helmet constructed with an ultra-high dielectric constant (uHDC; εr ~ 1000) materials that can be inserted into standard receive head-coils. METHODS: A helmet conformal to a standard human head constructed with uHDC materials was characterized through electromagnetic simulations and experimental work. The signal-to-noise ratio (SNR), transmit efficiency, and power deposition with the uHDC helmet inserted within a 20-channel head coil were measured in vivo and compared with a 64-channel head coil and the 20-channel coil without the helmet. Seven healthy volunteers were analyzed. RESULTS: Simulation and in vivo experimental results showed that transmit efficiency was improved by nearly 3 times within localized regions for a quadrature excitation, with a measured global increase of 58.21 ± 6.54% over 7 volunteers. The use of a parallel transmit spokes pulse compensated for severe degradation of B 1 + homogeneity, at the expense of higher global and local specific absorption rate levels. A SNR histogram analysis with statistical testing demonstrated that the uHDC helmet enhanced a 20-channel head coil to the level of the 64-channel head coil, with the improvements mainly within the cortical brain regions. CONCLUSION: A prototype uHDC helmet enhanced the SNR of a standard head coil to the level of a high density 64-channel coil, although transmit homogeneity was compromised. Further improvements in SNR may be achievable with optimization of this technology, and could be a low-cost approach for future radiofrequency engineering work in the brain at 3T.

15.
Sci Total Environ ; 697: 134097, 2019 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-31484090

RESUMO

Heavy metals inevitably cause invisible or visible damage to plants, leading to significant economic losses. Therefore, it is necessary to develop a method for timely monitoring the damage of plants under the stress of heavy metals. Here, vitronectin-like proteins (VN) on the surface of plant cells is as an important biomarker for monitoring damage of plants under the stress of heavy metals. A living plant cell-based biosensor is constructed to monitor invisible damage of plant cells induced by cadmium [Cd(II)] or lead [Pb(II)]. To fabricate this sensor, l-cysteine was first modified on the glassy carbon electrode followed by the modification of anti-IgG-Au antibody. Then, the living plant cells, incubated with the anti-VN, were modified onto the electrode. The sensor worked by determining the change in electrochemical impedance. Cd(II) and Pb(II) was detected in the linear dynamic range of 45-210 and 120-360 µmol·L-1, respectively. And the detection limit of Cd(II) and Pb(II) of this biosensor was 18.5 nmol·L-1 [with confidence interval (95%) 18.4-18.6 nmol·L-1] and 25.6 nmol·L-1 [with confidence interval (95%) 25.4-25.8 nmol·L-1], respectively. In both Arabidopsis and soybean, when the content of VN increased by about 20 times under the stress of Cd(II) or Pb(II), which means when the electron-transfer resistance increased by 35%, chlorophyll content showed significant decrease about 17%. Therefore, by establishing a quantitative relationship among the content of biomarker, the electron-transfer resistance and chlorophyll content in plant cells, the invisible damage of plants under the stress of heavy metals was detected. These results can provide a reference method for early-onset warning systems for heavy metal pollution in the environment.

16.
Nanotechnology ; 30(46): 465701, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31476136

RESUMO

In this study, the effect on the conductance of polymer nanocomposites considering quantum tunneling resistance is investigated with respect to the chirality of carbon nanotubes (CNTs) and uncertainties in the geometric parameters of CNTs by using Monte Carlo simulations. The random spatial placement for CNTs was accomplished with a one-dimensional line segment and the periodic boundary conditions were applied to CNTs in the two-dimensional representative volume element. Intersection points between each CNT were calculated to obtain connectivity lists of the connected network path. Both the intrinsic resistance of the CNT and the inter-CNT tunneling resistance were considered in this model. In addition, the in-house code developed was validated by comparison with several experimental datasets from the literature. Unlike past studies, uncertainties in the chiral index of single-wall CNTs concerning armchair and zig-zag structures have been considered here and the electrical conductivity and percolation threshold are predicted.

17.
Kaohsiung J Med Sci ; 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31483954

RESUMO

It has demonstrated that miR-22 overexpression can suppress the inflammation process of rheumatoid arthritis (RA) in synoviocytes. But, the underlying mechanism of miR-22 expression in regulating RA is still not well illustrated. In this study, we investigated the functional role and underlying mechanism of miR-22 in regulating RA. Human RA fibroblast-like synoviocyte (FLS) cell line MH7A cells was transfected by miR-22 mimic and its control. CCK8 was utilized to detect cell proliferation. Cell apoptosis was analyzed by flow cytometry. MH7A cells stimulating with interleukin-1ß (IL-1ß) were transfected with miR-22 mimic. Quantitative real time polymerase chain reaction (qRT-PCR) and western blot assays were utilized to detect mRNA and protein expression. miR-22 targets were predicted and validated by Targetscan and luciferase reporter assay. We revealed that miR-22 showed downregulated expression in MH7A after stimulation with IL-1ß. Additionally, miR-22 overexpression suppressed the proliferation and facilitated apoptosis in MH7A cells. IL6R was a target of miR-22. Besides, miR-22 overexpression inhibited the expression of IL6R and also suppressed inflammatory pathway NF-κB. These results indicated that miR-22 overexpression could restrain the activity of inflammation cells in RA by targeting IL6R and might be concerned with the inhibition of NF-κB pathway.

18.
Cell Mol Immunol ; 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31511639

RESUMO

The mitochondrial virus-induced signaling adaptor (VISA, also called mitochondrial antiviral signaling, MAVS) protein is a central adaptor in the innate immune response to cytosolic viral RNA. Viral infection causes the aggregation of VISA, which is important for its recruitment of downstream signaling components. How VISA aggregation is regulated remains unknown. Here, we found that sorting nexin 8 (SNX8) is a positive regulator of the RNA virus-triggered induction of downstream effector genes and innate immune response. The brains and lungs of Snx8-/- mice infected with RNA viruses exhibited lower serum cytokine levels and higher viral titers than those of wild-type mice, resulting in higher lethality. Mechanistically, viral infection induced the translocation of SNX8 from the cytosol to mitochondria and its increased association with VISA, leading to VISA aggregation, its recruitment of downstream signaling components and the induction of downstream antiviral genes. Our findings suggest that SNX8 is a critical component of the RIG-I-like receptor (RLR)-mediated innate immune response by modulating VISA aggregation and activation.

19.
J Exp Clin Cancer Res ; 38(1): 391, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31488180

RESUMO

BACKGROUND: Clinically, prostate cancer (PCa) exhibits a high avidity to metastasize to bone. Myc-associated zinc-finger protein (MAZ) is a well-documented oncogene involved in the progression and metastasis of multiple cancer types, even in PCa. However, the clinical significance and biological roles of MAZ in bone metastasis of PCa remain unclear. METHODS: MAZ expression was examined in PCa tissues with bone metastasis, PCa tissues without bone metastasis and metastatic bone tissues by real-time PCR and immunohistochemistry (IHC), respectively. Statistical analysis was performed to evaluate the clinical correlation between MAZ expression and clinicopathological features and bone metastasis-free survival in PCa patients. Biological roles of MAZ in bone metastasis of PCa were investigated both in vitro by transwell assay, and in vivo by a mouse model of left cardiac ventricle inoculation. The bioinformatics analysis, western blot, pull-down assays, chromatin immunoprecipitation (ChIP) and luciferase reporter assays were applied to demonstrate and examine the relationship between MAZ and its potential downstream signalling pathway. TaqMan copy number assay was performed to identify the underlying mechanism responsible for MAZ overexpression in PCa tissues. RESULTS: MAZ expression is elevated in PCa tissues with bone metastasis compared with that in PCa tissues without bone metastasis, and is further increased in metastatic bone tissues. High expression of MAZ positively correlates with poor overall and bone metastasis-free survival in PCa patients. Upregulating MAZ elevates, while silencing MAZ represses the invasion and migration abilities of PCa cells in vitro and bone metastasis ability in vivo. Our results further reveal that MAZ promotes bone metastasis of PCa dependent on KRas signalling, although MAZ transcriptionally upregulates KRas and HRas expression, where the Ral guanine nucleotide exchange factor (RalGEF) signaling is responsible for the different roles of KRas and HRas in mediating the pro-bone metastasis of MAZ in PCa. Finally, our results indicate that recurrent gains contribute to MAZ overexpression in a small portion of PCa tissues. CONCLUSION: These results indicate that the MAZ/Kras/ RalGEF signalling axis plays a crucial role in promoting PCa cell bone metastasis, suggesting a potential therapeutic utility of MAZ in bone metastasis of PCa.

20.
J Exp Clin Cancer Res ; 38(1): 387, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31488195

RESUMO

In the original publication of this article [1], the Fig. 7 is wrong, but does not affect discussions and conclusions drawn in the article.

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