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1.
Biochem Cell Biol ; 98(3): 396-404, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31800303

RESUMO

Prostate cancer (PCa) is the second leading cause of death in men, and current studies have shown that circular RNAs (circRNAs) play important roles in its occurrence and development. Detection of circRNAs in PCa cells showed that circ_KATNAL1 is down-regulated, mainly located in the cytoplasm, and contains multiple binding sites of miR-145-3p, which is an anticancer miRNA. RNA immunoprecipitation with anti-AGO2 antibody, RNA pull-down assays with biotin-labeled circ_KATNAL1 probe or an miR-145-3p mimic, and dual luciferase reporter gene assays confirmed that circ_KATNAL1 binds directly to miR-145-3p in cells, and that WISP1, which is highly expressed in many types of tumors, is an important target gene of miR-145-3p. Circ_KATNAL1 and miR-145-3p promote each other's expression, and down-regulate the expression of the target gene WISP1. Both circ_KATNAL1 and miR-145-3p inhibit cell proliferation, invasiveness, and migration, down-regulate the expression of MMP-2 and MMP-9, promote cell apoptosis and the activation of caspase-3, caspase-8, caspase-9, and PARP, whereas WISP1 has the opposite effect, and the above-mentioned functions of circ_KATNAL1 were achieved through the miR-145-3p/WISP1 pathway. Therefore, circ_KATNAL1 plays an anticancer role in PCa cells through the miR-145-3p/WISP1 pathway, which could be an important target for the diagnosis and treatment of PCa.


Assuntos
Proteínas de Sinalização Intercelular CCN/metabolismo , Regulação Neoplásica da Expressão Gênica , Katanina/metabolismo , MicroRNAs/metabolismo , Neoplasias da Próstata/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , RNA Circular/metabolismo , Antineoplásicos/farmacologia , Apoptose , Sítios de Ligação , Linhagem Celular Tumoral , Movimento Celular , Núcleo Celular/metabolismo , Proliferação de Células , Citoplasma/metabolismo , Humanos , Imunoprecipitação , Masculino , Invasividade Neoplásica
2.
Mol Carcinog ; 59(8): 897-907, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32319143

RESUMO

Lactate dehydrogenase isozyme (LDH) is a tetramer constituted of two isoforms, LDHA and LDHB, the expression of which is associated with cell metabolism and cancer progression. Our previous study reveals that CC-chemokine ligand-18 (CCL18) is involved in progression of prostate cancer (PCa).This study aims to investigate how CCL18 regulates LDH isoform expression, and therefore, contributes to PCa progression. The data revealed that the expression of LDHA was upregulated and LDHB was downregulated in PCa cells by CCL18 at both messenger RNA and protein levels. The depletion of CCR8 reduced the ability of CCL18 to promote the proliferation, migration, and lactate production of PCa cells. Depletion of a CCR8 regulated transcription factor, ARNT, significantly reduced the expression of LDHA. In addition, The Cancer Genome Atlas dataset analyses revealed a positive correlation between CCR8 and ARNT expression. Two dimension difference gel electrophoresis revealed that the LDHA/LDHB ratio was increased in the prostatic fluid of patients with PCa and PCa tissues. Furthermore, increased LDHA/LDHB ratio was associated with poor clinical outcomes of patients with PCa. Together, our results indicate that the CCR8 pathway programs LDH isoform expression in an ARNT dependent manner and that the ratio of LDHA/LDHB has the potential to serve as biomarkers for PCa diagnosis and prognosis.


Assuntos
Translocador Nuclear Receptor Aril Hidrocarboneto/metabolismo , Biomarcadores Tumorais/metabolismo , Quimiocinas CC/metabolismo , Regulação Neoplásica da Expressão Gênica , L-Lactato Desidrogenase/metabolismo , Neoplasias da Próstata/patologia , Receptores CCR8/metabolismo , Apoptose , Translocador Nuclear Receptor Aril Hidrocarboneto/genética , Biomarcadores Tumorais/genética , Proliferação de Células , Quimiocinas CC/genética , Humanos , Isoenzimas , L-Lactato Desidrogenase/genética , Masculino , Prognóstico , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Receptores CCR8/genética , Taxa de Sobrevida , Células Tumorais Cultivadas
3.
Cell Biol Int ; 44(4): 1037-1045, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31903637

RESUMO

The occurrence and development of prostate cancer (PCa) is complex, and the related mechanism is not fully understood. Current studies have found that extracellular vesicles (EVs) and circular RNAs (circRNAs) have important functions in various tumours and other diseases. In this study, the detection of circRNAs in PCa showed that circ_SLC19A1 was increased in PCa cells and their secreted EVs. EVs with high expression of circ_SLC19A1 could be taken up by PCa cells, which promoted cell proliferation and invasion. The sequence of circ_SLC19A1 contained multiple binding sites for miR-497, and circ_SLC19A1 could bind directly to miR-497 in cells. The expression of miR-497 was downregulated in PCa cells, while the expression of its target gene septin 2 (SEPT2) was upregulated significantly. Transfection of circ_SLC19A1 small interfering RNA (siRNA) or miR-497 mimics could significantly inhibit the expression of SEPT2 and the phosphorylation of extracellular signal-regulated kinase 1 and 2 (ERK1/2). After co-transfection of circ_SLC19A1 siRNA and miR-497 inhibitors or SEPT2 overexpression vector, the expression of SEPT2 and ERK1/2 phosphorylation levels showed no significant changes. Similar results were obtained with co-transfection of miR-497 mimics and the SEPT2 overexpression vector. Therefore, cancer cells can regulate the expression of SEPT2 through miR-497 by secreting EVs with high expression of circ_SLC19A1, thus affecting the activation of the downstream ERK1/2 pathway and ultimately regulating PCa cell growth and invasion. Therefore, EV-derived circ_SLC19A1 plays an important regulatory role in PCa and may be an important target for PCa prevention and treatment.


Assuntos
Vesículas Extracelulares/fisiologia , Neoplasias da Próstata/metabolismo , RNA Circular/genética , Proteína Carregadora de Folato Reduzido/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , MicroRNAs/metabolismo , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Septinas/metabolismo
6.
Mol Cancer ; 16(1): 48, 2017 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-28241827

RESUMO

BACKGROUND: Even though aberrant expression of microRNA (miR)-30d has been reported in prostate cancer (PCa), its associations with cancer progression remain contradictory. The aim of this study was to investigate clinical significance, biological functions and underlying mechanisms of miR-30d deregulation in PCa. METHODS: Involvement of miR-30d deregulation in malignant phenotypes of PCa was demonstrated by clinical sample evaluation, and in vitro and in vivo experiments. The mechanisms underlying its regulatory effect on tumor angiogenesis were determined. RESULTS: miR-30d over-expression was observed in both PCa cells and clinical specimens. High-miR-30d was distinctly associated with high pre-operative PSA and Gleason score, advanced clinical and pathological stages, positive metastasis and biochemical recurrence (BCR), and reduced overall survival of PCa patients. Through gain- and loss-of-function experiments, we found that miR-30d promoted PCa cell proliferation, migration, invasion, and capillary tube formation of endothelial cells, as well as in vivo tumor growth and angiogenesis in a mouse model. Simulation of myosin phosphatase targeting subunit 1 (MYPT1), acting as a direct target of miR-30d, antagonized the effects induced by miR-30d up-regulation in PCa cells. Notably, miR-30d/MYPT1 combination was identified as an independent factor to predict BCR of PCa patients. Furthermore, miR-30d exerted its pro-angiogenesis function, at least in part, by inhibiting MYPT1, which in turn, increased phosphorylation levels of c-JUN and activated VEGFA-induced signaling cascade in endothelial cells. CONCLUSIONS: miR-30d and/or its target gene MYPT1 may serve as novel prognostic markers of PCa. miR-30d promotes tumor angiogenesis of PCa through MYPT1/c-JUN/VEGFA pathway.


Assuntos
MicroRNAs/genética , Fosfatase de Miosina-de-Cadeia-Leve/metabolismo , Neovascularização Patológica/genética , Neovascularização Patológica/metabolismo , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Proteínas Proto-Oncogênicas c-jun/metabolismo , Transdução de Sinais , Fator A de Crescimento do Endotélio Vascular/metabolismo , Animais , Biomarcadores Tumorais , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células , Modelos Animais de Doenças , Progressão da Doença , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Xenoenxertos , Humanos , Masculino , Camundongos , Fosfatase de Miosina-de-Cadeia-Leve/genética , Prognóstico , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Interferência de RNA
7.
Int J Cancer ; 135(3): 541-50, 2014 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-24382668

RESUMO

Our previous microarray data showed that microRNA-224 (miR-224) was downregulated in human prostate cancer (PCa) tissues compared with adjacent benign tissues. However, the underlying mechanisms by which miR-224 is involved in PCa remain unclear. In this study, we identified TRIB1 as a target gene of miR-224. Forced expression of miR-224 suppressed PCa cell proliferation, invasion and migration, and promoted cell apoptosis by downregulating TRIB1. Moreover, the expression level of miR-224 in PCa tissues was negatively correlated with that of TRIB1. miR-224 downregulation was frequently found in PCa tissues with metastasis, higher PSA level and clinical stage, whereas TRIB1 upregulation was significantly associated with metastasis. Both miR-224 downregulation and TRIB1 upregulation were significantly associated with poor biochemical recurrence-free survival of patients with PCa. In conclusion, these findings reveal that the aberrant expression of miR-224 and TRIB1 may promote PCa progression and have potentials to serve as novel biomarkers for PCa prognosis.


Assuntos
Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , MicroRNAs/genética , Próstata/metabolismo , Neoplasias da Próstata/genética , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Adulto , Idoso , Idoso de 80 Anos ou mais , Apoptose , Biomarcadores Tumorais/metabolismo , Western Blotting , Movimento Celular , Proliferação de Células , Progressão da Doença , Citometria de Fluxo , Humanos , Técnicas Imunoenzimáticas , Hibridização In Situ , Peptídeos e Proteínas de Sinalização Intracelular/genética , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Próstata/patologia , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Taxa de Sobrevida , Análise Serial de Tecidos , Células Tumorais Cultivadas
8.
Mol Biol Rep ; 41(5): 2779-88, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24452717

RESUMO

MicroRNA-30c (miR-30c) acts as a tumor suppressor or a tumor promoter in various human malignancies. However, the involvement of miR-30c in prostate cancer (PCa) is still unclear. The aim of this study was to investigate the molecular function and the clinical significance of miR-30c in PCa. Expression levels of miR-30c in PCa tissues and cells were detected by quantitative real-time-PCR (qRT-PCR). Additionally, the associations of miR-30c expression with clinicopathological features and prognosis in PCa patients were analyzed. The potential role of miR-30c in tumorigenesis of PCa cells was further evaluated by in vitro cell assays. MiR-30c was significantly down-regulated in PCa tissues and cells compared with the corresponding controls (P<0.05). In addition, the downregulation of miR-30c in PCa tissues was significantly associated with higher Gleason score (P=0.009), advanced pathological stage (P=0.016) and biochemical recurrence (P=0.034). Moreover, Kaplan-Meier survival analysis showed that the reduced expression of miR-30c was correlated with shorter biochemical recurrence-free survival (P=0.023). The multivariate analysis also identified miR-30c as an independent prognostic predictor for biochemical recurrence-free survival in patients with PCa. Furthermore, the enforced expression of miR-30c suppressed proliferation, migration and invasion of PCa cells in vitro. Our data indicated the involvement of miR-30c in PCa progression and suggested its potential role as an independent predictor of biochemical recurrence in PCa. On cellular level, miR-30c may function as a tumor suppressor for PCa cells by inhibiting tumor cell proliferation, migration and invasion.


Assuntos
Genes Supressores de Tumor , MicroRNAs/genética , Neoplasias da Próstata/genética , Adulto , Idoso , Movimento Celular/genética , Proliferação de Células , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Antígeno Prostático Específico/metabolismo , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Curva ROC , Recidiva
9.
BMC Genomics ; 14: 757, 2013 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-24191917

RESUMO

BACKGROUND: Our recent study showed the global physiological function of the differentially expressed genes of prostate cancer in Chinese patients was different from that of other non-Chinese populations. microRNA are estimated to regulate the expression of greater than 60% of all protein-coding genes. To further investigate the global association between the transcript abundance of miRNAs and their target mRNAs in Chinese patients, we used microRNA microarray approach combined with bioinformatics and clinical-pathological assay to investigate the miRNA profile and evaluate the potential of miRNAs as diagnostic and prognostic markers in Chinese patients. RESULTS: A total of 28 miRNAs (fold change ≥ 1.5; P ≤ 0.05) were differentially expressed between tumor tissue and adjacent benign tissue of 4 prostate cancer patients.10 top Differentially expressed miRNAs were validated by qRT-PCR using all 20 tissue pairs. Compared to the miRNA profile of non-Chinese populations, the current study showed that miR-23b, miR-220, miR-221, miR-222, and miR-205 maybe common critical therapeutic targets in different populations. The integrated analysis for mRNA microarray and miRNA microarray showed the effects of specifically inhibiting and/or enhancing the function of miRNAs on the gene transcription level. The current studies also identified 15 specific expressed miRNAs in Chinese patients. The clinical feature statistics revealed that miR-374b and miR-19a have significant correlations with clinical-pathological features in Chinese patients. CONCLUSIONS: Our findings showed Chinese prostate cancer patients have a common and specific miRNA expression profile compared with non-Chinese populations. The miR-374b is down-regulated in prostate cancer tissue, and it can be identified as an independent predictor of biochemical recurrence-free survival.


Assuntos
Biomarcadores Tumorais/biossíntese , MicroRNAs/biossíntese , Recidiva Local de Neoplasia/genética , Neoplasias da Próstata/genética , Idoso , Povo Asiático , Intervalo Livre de Doença , Regulação Neoplásica da Expressão Gênica , Estudos de Associação Genética , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , RNA Mensageiro/genética
10.
Mol Biol Rep ; 40(5): 3799-805, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23283744

RESUMO

The ErbB3 binding protein 1 (Ebp1) represents a downstream effector of the ErbB signaling network and has been demonstrated to be a potent tumor suppressor in various human malignancies, however, its involvement in human bladder cancer is still unclear.To investigate the clinical significance and potential role of ErbB3 binding protein 1 (Ebp1) in bladder cancer. Ebp1 expression at protein and gene levels in 52 surgically removed bladder cancer specimens as well as 21 adjacent normal bladder specimens were respectively detected by immunohistochemistry and qRT-PCR. The association of Ebp1 protein expression with the clinicopathological features of bladder cancer was also statistically analyzed. Its roles in bladder cancer cell line were further evaluated. The expression level of Ebp1 protein and gene in bladder cancer tissues was significantly lower than that in adjacent normal bladder tissues (P < 0.01). When categorized into low vs. high expression, the down-regulation of Ebp1 protein was associated with the advanced pathologic stage (P = 0.036) and the high histologic grade (P = 0.001) of patients with bladder cancer. Moreover, following the transfection of Ebp1 in bladder cancer cells, not only cell proliferation and cell invasion decreased significantly, but also the cell cycle was blocked at G0/G1 stage. Our data suggest for the first time that the down-regulation of Ebp1 closely correlates with advanced clinicopathological characteristics of human bladder cancer. Furthermore, Ebp1 plays an important role in the bladder cancer cells' proliferation by regulating the cancer cell cycle from G0/G1 to S.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas de Ligação a RNA/metabolismo , Neoplasias da Bexiga Urinária/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Adenoviridae/genética , Idoso , Idoso de 80 Anos ou mais , Pontos de Checagem do Ciclo Celular/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células , Progressão da Doença , Regulação para Baixo , Feminino , Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Vetores Genéticos/genética , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Proteínas de Ligação a RNA/genética , Transdução Genética , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia
11.
Food Sci Nutr ; 11(8): 4773-4780, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37576036

RESUMO

The estimated glomerular filtration rate (eGFR) is a comprehensive index that is widely used to assess renal function. Although studies have confirmed a correlation between eGFR and dietary vitamin C, the impact of varying levels of vitamin C on eGFR remains unclear. Additionally, the interaction between dietary magnesium intake and vitamin C concentration on eGFR is not well understood. As such, the objective of this study was to investigate the relationship between dietary magnesium intake and vitamin C in relation to eGFR. This study analyzed the data of consecutive NHANES from 2005 to 2018. We included 17,633 participants aged 20 or older and used multiple linear regression analysis to evaluate the relationship between dietary vitamin C and eGFR. Dietary Mg intake from experimental data was dichotomized into a low dietary Mg intake group (≤254 mg/day) and a normal dietary Mg intake group (>254 mg/day). To evaluate the impact of dietary magnesium intake on eGFR, a multivariable linear regression was conducted utilizing an interaction test between dietary vitamin C and eGFR. We discovered a positive association between dietary vitamin C content and eGFR. The relationship between dietary vitamin C levels and eGFR differed between individuals with low Mg intake and those with normal Mg intake (ß: 2.96 95% CI:1.63 ~ 4.29 vs. ß: 1.05 95% CI: -0.15 to 2.25), and the positive association of high dietary vitamin C content with eGFR was stronger in the low Mg intake group. Furthermore, we observed that dietary magnesium intake significantly altered the positive association between dietary vitamin C and eGFR (interaction value of 0.020). Our experimental study revealed that the interaction between dietary magnesium and dietary vitamin C can significantly impact eGFR. This finding carries significant implications for the treatment of diseases resulting from abnormal eGFR, as well as the selection of clinically relevant drugs.

12.
BMC Cancer ; 12: 248, 2012 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-22703285

RESUMO

BACKGROUND: SOX genes play an important role in a number of developmental processes. Potential roles of SOXs have been demonstrated in various neoplastic tissues as tumor suppressors or promoters depending on tumor status and types. The aim of this study was to investigate the involvement of SOXs in the progression and prognosis of human prostate cancer (PCa). METHODS: The gene expression changes of SOXs in human PCa tissues compared with non-cancerous prostate tissues was detected using gene expression microarray, and confirmed by real-time quantitative reverse transcriptase-polymerase chain reaction (QRT-PCR) analysis and immunohositochemistry. The roles of these genes in castration resistance were investigated in LNCaP xenograft model of PCa. RESULTS: The microarray analysis identified three genes (SOX7, SOX9 and SOX10) of SOX family that were significantly dis-regulated in common among four PCa specimens. Consistent with the results of the microarray, differential mRNA and protein levels of three selected genes were found in PCa tissues by QRT-PCR analysis and immunohistochemistry. Additionally, we found that the immunohistochemical staining scores of SOX7 in PCa tissues with higher serum PSA level (P = 0.02) and metastasis (P = 0.03) were significantly lower than those with lower serum PSA level and without metastasis; the increased SOX9 protein expression was frequently found in PCa tissues with higher Gleason score (P = 0.02) and higher clinical stage (P < 0.0001); the down-regulation of SOX10 tend to be found in PCa tissues with higher serum PSA levels (P = 0.03) and advanced pathological stage (P = 0.01). Moreover, both univariate and multivariate analyses showed that the down-regulation of SOX7 and the up-regulation of SOX9 were independent predictors of shorter biochemical recurrence-free survival. Furthermore, we discovered that SOX7 was significantly down-regulated and SOX9 was significantly up-regulated during the progression to castration resistance. CONCLUSIONS: Our data offer the convince evidence that the dis-regulation of SOX7, SOX9 and SOX10 may be associated with the aggressive progression of PCa. SOX7 and SOX9 may be potential markers for prognosis in PCa patients. Interestingly, the down-regulation of SOX7 and the up-regulation of SOX9 may be important mechanisms for castration-resistant progression of PCa.


Assuntos
Neoplasias da Próstata/genética , Fatores de Transcrição SOX/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Progressão da Doença , Perfilação da Expressão Gênica , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Orquiectomia , Prognóstico , Hiperplasia Prostática , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Reprodutibilidade dos Testes , Fatores de Transcrição SOX/metabolismo , Fatores de Transcrição SOX9/genética , Fatores de Transcrição SOX9/metabolismo , Fatores de Transcrição SOXE/genética , Fatores de Transcrição SOXE/metabolismo , Fatores de Transcrição SOXF/genética , Fatores de Transcrição SOXF/metabolismo
13.
Dis Markers ; 2022: 8724035, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35548776

RESUMO

Background: In our previous research, we developed a 32-gene risk index model that may be utilized as a robust prognostic method for predicting prostate cancer (PCa) recurrence after surgery. Among the 32 genes, the Fifth Ewing Variant (FEV) gene was one of the top downregulated genes in relapsed PCa. However, current understanding of the FEV gene and its involvement in PCa is limited. Methods: FEV mRNA expression was analyzed and correlated to clinical outcomes in PCa patients who underwent prostatectomy at the Massachusetts General Hospital. Specimens from tissue microarray (TMA) including 102 prostate cancer patients were analysis for the expression of FEV. Meanwhile, FEV expression profiles were also assessed in PCa cell lines and in BPH-1 prostate epithelial cells using western blotting and quantitative reverse transcription-PCR (qRT-PCR). Furthermore, we transfected LNCaP and PC-3 cells with either an empty vector or full-length FEV gene and performed in vitro cell functional assays. The part FEV plays in tumor xenograft growth was also assessed in vivo. Results: Of the 191 patients included in this study base on the DASL dataset, 77 (40.3%) and 24 (13.6%), respectively, developed prostate-specific antigen (PSA) relapse and metastasis postradical prostatectomy. Significant FEV downregulation was observed in PCa patients showing PSA failure and metastasis. The protein expression of FEV was significantly negatively correlated with the Gleason score and pathological stage in prostate cancer tissues. Similarly, FEV expression significantly decreased in all PCa cell lines relative to BPH-1 (all P < 0.05). Functional assays revealed that FEV expression markedly inhibited PCa cell growth, migration, and invasion, which in turn significantly repressed the growth of tumor xenografts in vivo. Conclusion: The results of this study suggest an association between downregulated FEV expression and PSA relapse in PCa patients. In addition, FEV may act as a tumor suppressor in PCa.


Assuntos
Proteínas de Ligação a DNA , Hiperplasia Prostática , Neoplasias da Próstata , Fatores de Transcrição , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Recidiva Local de Neoplasia/patologia , Antígeno Prostático Específico , Prostatectomia/métodos , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia
14.
Cell Signal ; 59: 152-162, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30926388

RESUMO

Immunotherapy has made great breakthroughs in the field of cancer. However, the immunotherapeutic effect of prostate cancer is unsatisfactory. We found that the expression of TRIB1 was significantly correlated with the infiltration of CD163+ macrophages in prostate cancer. This study focused on the effects of TRIB1 on macrophage polarization in the immune microenvironment of prostate cancer. RNA sequencing analysis demonstrated that TRIB1 has significant effects on the regulation of the nuclear factor (NF)-κB signaling pathway and downstream cytokines. Flow cytometry and enzyme-linked immunosorbent assay were used to examine THP-1 cells cultured in conditioned medium from prostate cancer cells overexpressing TRIB1 and showed that overexpression of TRIB1 promoted the secretion of CXCL2 and interleukin (IL)8 by PC3 cells, which increased the secretion of IL12 by THP-1 cells as well as the expression of CD163 on THP-1 cells. IKB-zeta, regulated by TRIB1, was expressed in PC3 cells but was barely detectable in DU145 cells. The reductions in CXCL2 and IL8 by the inhibition of TRIB1 were rescued by the deletion of IKB-zeta. Here we showed that TRIB1 promoted the secretion of cytokines from prostate cancer cells and induced the differentiation of monocytes/macrophages into M2 macrophages.


Assuntos
Peptídeos e Proteínas de Sinalização Intracelular/fisiologia , Macrófagos/imunologia , Neoplasias da Próstata/metabolismo , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Microambiente Tumoral/imunologia , Animais , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Quimiocina CXCL2/imunologia , Humanos , Ativação de Macrófagos , Macrófagos/citologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , NF-kappa B/imunologia , Células PC-3 , Proteínas Serina-Treonina Quinases/fisiologia , Receptores de Superfície Celular/metabolismo , Células THP-1
15.
Int J Oncol ; 48(4): 1650-8, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26891801

RESUMO

Increased expression of E2F1 has been reported to be associated with tumor growth and cell survival of prostate cancer (PCa). However, its roles and mechanisms on PCa have not been fully elucidated. The present study found that E2F1 overexpression in PCa tissues was significantly associated with high Gleason score (P=0.01) and advanced pathological stage (P=0.02). In addition, PCa patients with high E2F1 expression more frequently had shorter biochemical recurrence-free survival (P=0.047) than those with low E2F1 expression. Then, we confirmed that the knock-down of E2F1 expression was able to inhibit cell cycle progression, invasion and migration of PCa cell lines in vitro, along with tumor xenograft growth and epithelial-to-mesenchymal transition (EMT) in vivo. Moreover, we identified CD147 as a novel interaction partner for E2F1 through bio-informatic binding site prediction, combined with chromatin immunoprecipitation-PCR (ChIP-PCR) and western blot analysis. Taken together, our data delineate an as yet unrecognized function of E2F1 as enhancer of tumor invasion and migration of PCa via regulating the expression of CD147 in PCa. Importantly, E2F1 may function as a biomarker that can differentiate patients with biochemical recurrent and non-biochemical recurrent disease following radical prostatectomy, highlighting its potential as a therapeutic target.


Assuntos
Basigina/metabolismo , Fator de Transcrição E2F1/metabolismo , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Animais , Basigina/genética , Sítios de Ligação , Linhagem Celular Tumoral , Movimento Celular , Fator de Transcrição E2F1/química , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos , Gradação de Tumores , Invasividade Neoplásica , Prognóstico , Neoplasias da Próstata/genética , Análise de Sobrevida
16.
Onco Targets Ther ; 9: 2211-20, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27143916

RESUMO

BUB1 mitotic checkpoint serine/threonine kinase B (BUB1B) is a member of the spindle assembly checkpoint protein family, which has been proven to be associated with many kinds of cancers. The aim of this study was to investigate whether BUB1B was correlated with progression and prognosis in patients with prostate cancer (PCa) and how BUB1B regulated the proliferation, migration, and invasion of PCa cell lines. Compared to benign prostate cells and tissues, both messenger RNA and protein expressions of BUB1B were statistically increased in PCa cell lines and tumor tissues. In vitro studies revealed that BUB1B overexpression enhanced the proliferation, migration, and invasion ability of PCa cell lines, whereas depletion of BUB1B did not affect the cell functions. Microarray analysis showed the positive staining of BUB1B was upregulated in the higher Gleason score group, which also correlated with advanced clinicopathological stage, higher serum prostate-specific antigen, metastasis, overall survival, and prostate-specific antigen failure. Furthermore, the survival analysis indicated that high expression of BUB1B was an independent predictor for shorter biochemical recurrence-free survival, which had no effect on overall survival. BUB1B plays an important role in tumor growth and progression, which can lead to its use as a potential biomarker for the diagnosis and prognosis of PCa.

17.
Int J Biol Macromol ; 81: 615-23, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26314905

RESUMO

Roles and mechanisms of cell cycle-specific transcription factor E2F1 on prostate cancer (PCa) have not been fully elucidated. To address this problem, we here identified PDZ-binding kinase (PBK) as a direct target for E2F1 through bioinformatics binding site prediction, combined with chromatin immunoprecipitation-PCR (ChIP-PCR), quantitative (Q)-PCR and Western blot analysis. Then, we observed that the knockdown of both E2F1 and PBK could suppress cell proliferation, invasion and migration of PCa cell lines in vitro. Based on Taylor dataset, we found that PBK upregulation occurred more frequently in PCa patients with the older age of patients (P=0.044), the higher Gleason score (P<0.001), the advanced clinical pathological stage (P=0.019), the presence of metastasis (P=0.008), the overall survival (P<0.001) and PSA failure (P=0.004). More interestingly, the survival analysis identified PBK as an independent factor for predicting the biochemical recurrence-free survival of PCa patients (P=0.041). Taken together, these findings offer the convincing evidence for the first time that the overexpression of PBK may lead to high malignant phenotype in PCa cells via the regulation of E2F1. PBK may function as a biomarker that can differentiate patients with biochemical recurrent and non-biochemical recurrent disease following radical prostatectomy, highlighting its potential as a therapeutic target.


Assuntos
Fator de Transcrição E2F1/metabolismo , Regulação Neoplásica da Expressão Gênica , Quinases de Proteína Quinase Ativadas por Mitógeno/genética , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Fenótipo , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Idoso , Idoso de 80 Anos ou mais , Sequência de Bases , Sítios de Ligação , Linhagem Celular Tumoral , Movimento Celular , Sobrevivência Celular , Citoproteção , Progressão da Doença , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Motivos de Nucleotídeos , Prognóstico , Regiões Promotoras Genéticas , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Ligação Proteica
18.
Med Oncol ; 31(1): 820, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24338276

RESUMO

The aim of this study was to investigate the associations of myosin light chain (MYL9) downregulation with tumor progression and prognosis in patients with prostate cancer (PCa). MYL9 protein expression in human PCa and non-cancerous prostate tissues was detected by Western blot and immunohistochemistry analyses, which was validated by microarray-based Taylor data at mRNA level. Then, the associations of MYL9 expression with clinicopathological features and clinical outcome of PCa patients were statistically analyzed. Both Western blot and immunohistochemistry analyses found that MYL9 expression was significantly decreased (both P < 0.001) in PCa tissues compared with those in non-cancerous prostate tissues. In addition, MYL9 was mainly expressed in the cytoplasm of stromal cells of prostate tissues, and the decreased expression of MYL9 in PCa tissues was significantly correlated with the older age of patients (P = 0.011), the higher Gleason score (P < 0.001), the advanced pathological stage (P = 0.002), the presence of metastasis (P < 0.001) and PSA failure (P = 0.001). Furthermore, both univariate and multivariate analyses showed that the downregulation of MYL9 was an independent predictor of shorter overall survival (P = 0.026 and P = 0.009, respectively) and biochemical recurrence-free survival (P = 0.001 and P = 0.002, respectively). Our data strongly confirmed for the first time that the decreased expression of MYL9 may play an important role in tumor progression of PCa. More importantly, the downregulation of MYL9 may efficiently predict both overall and biochemical recurrence-free survivals in PCa patients.


Assuntos
Regulação Neoplásica da Expressão Gênica , Miosinas/metabolismo , Neoplasias da Próstata/metabolismo , Idoso , Progressão da Doença , Intervalo Livre de Doença , Humanos , Masculino , Pessoa de Meia-Idade , Miosinas/genética , Análise de Sequência com Séries de Oligonucleotídeos , Prognóstico , Próstata/metabolismo , RNA Mensageiro/metabolismo
19.
Med Oncol ; 30(1): 465, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23377984

RESUMO

The copy number gain of genes in chromosomal region 8q21-24 has been demonstrated to be associated with genesis and progression of prostate cancer (PCa). The aim of this study was to identify novel and effective molecular markers in this chromosomal region for PCa. The differentially expressed genes in PCa specimens were screened by gene microarray analysis, which was validated by RT-QPCR analysis. Then, the DNA qPCR analysis was carried out to detect the copy number changes of these differentially expressed genes. Moreover, the clinical significance of candidate markers (MYC and E2F5) in PCa were further determined. E2F5 and MYC were identified as candidate markers in PCa tissues and PCa cell lines. The DNA qPCR revealed the significant copy number gains of E2F5 and MYC in PCa tissues but not in PCa cell lines. In addition, Western blot analysis and immunohistochemical staining both found the significant higher expression of E2F5 and MYC proteins in PCa tissues than those in adjacent benign specimens (all P < 0.01). Moreover, the overexpression of E2F5 protein was significantly associated with a high Gleason score (P < 0.01), an advanced clinical stage (P = 0.01), a positive metastasis (P < 0.01) and PSA Failure (P < 0.01). The overexpression of MYC was more frequently found in PCa tissues with positive metastasis (P = 0.02) and PSA failure (P = 0.02). Interestingly, there was a close correlation in the expression level of MYC in PCa tissues with that of E2F5 (r ( s ) = 0.5, P ≤ 0.001). Our data offers the convincing evidence that the copy number gains of E2F5 and MYC may play an important role in genesis and progression of PCa. Especially, E2F5 may be a novel potential candidate marker for malignant PCa.


Assuntos
Biomarcadores Tumorais/genética , Cromossomos Humanos Par 8/genética , Fator de Transcrição E2F5/genética , Dosagem de Genes , Proteínas Oncogênicas/genética , Neoplasias da Próstata/genética , Idoso , Idoso de 80 Anos ou mais , Western Blotting , Linhagem Celular Tumoral , Aberrações Cromossômicas , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Proteína Oncogênica p55(v-myc)/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa
20.
FEBS Lett ; 586(16): 2451-8, 2012 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-22710126

RESUMO

To investigate the mechanism by which peroxiredoxin III (PRDX3) is altered in human prostate cancer (PCa), we used microRNA (miRNA) target prediction program and miRNA microarray to predict and identify miR-23b as a candidate miRNA that targets PRDX3. We showed that miR-23b suppresses PRDX3 protein expression in human DU145 cells under normal and hypoxic conditions. Additionally, the clinical significance of miR-23b and PRDX3 expression in PCa patients was also confirmed. In conclusion, our data suggest that the effects of PRDX3 in PCa progression may be caused by the regulation function of miR-23b, and consequently, miR-23b may be involved in the response of PCa cells to hypoxia stress.


Assuntos
Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , MicroRNAs/fisiologia , Peroxirredoxina III/biossíntese , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Idoso , Idoso de 80 Anos ou mais , Sequência de Bases , Linhagem Celular Tumoral , Progressão da Doença , Intervalo Livre de Doença , Perfilação da Expressão Gênica , Humanos , Hipóxia , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Dados de Sequência Molecular , Análise de Sequência com Séries de Oligonucleotídeos
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