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1.
Se Pu ; 37(8): 887-896, 2019 Aug 08.
Artigo em Chinês | MEDLINE | ID: mdl-31642260

RESUMO

Speckle type BTB/POZ protein (SPOP) is one of the most frequently mutated protein in prostate cancer. In this study, proteomics and metabolomics were integrated to study the effects of SPOP mutation on metabolism. First, LNCaP control (CON), SPOP wild-type (SPOP_WT), and SPOP mutation (SPOP_Y87N and SPOP_F133L) cells were subjected to a metabolomics study. The metabolomics data of LNCaP CON, SPOP_WT, SPOP_Y87N, and SPOP_F133L cells were evaluated by partial least squares-discriminant analysis (PLS-DA). Four groups could be clearly differentiated with an explanation ability of R2X=0.512, R2Y=0.616 and predictive ability of Q2=0.475. Totally, 36 differential metabolites were defined with variable importance for the projection (VIP) value > 1. Then, the 36 metabolites were subjected to one-way ANOVA analysis. Fumaric acid, malic acid, citric acid, aspartic acid, and asparagine were increased in LNCaP SPOP mutation cells compared to that in LNCaP SPOP_WT cells. Using a proteomics study, 909 differential proteins were found in LNCaP SPOP_Y87N and SPOP_F133L cells. MetaboAnalyst 3.0 was used to enrich metabolic pathways by using differential metabolites. KOBAS 3.0 was used to enrich metabolic pathways by using differential proteins. Both metabolomics and proteomics analysis showed that the tricarboxylic acid (TCA) cycle and aminoacyl-tRNA biosynthesis were significantly changed. To validate these findings, gas chromatography-mass spectrometry (GC-MS)-based metabolomics was performed in Du145 SPOP knock-out cells. The results indicated that the TCA cycle was activated in Du145 SPOP knock-out cells. Collectively, this study found that SPOP mutation significantly promoted TCA cycle in prostate cancer cells.


Assuntos
Domínio BTB-POZ , Metabolômica , Proteínas Nucleares/genética , Neoplasias da Próstata/genética , Proteômica , Proteínas Repressoras/genética , Linhagem Celular Tumoral , Ciclo do Ácido Cítrico , Humanos , Masculino , Redes e Vias Metabólicas , Mutação
2.
Adv Exp Med Biol ; 1164: 119-139, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31576545

RESUMO

Alternative splicing, the process of removing introns and joining exons of pre-mRNA, is critical for growth, development, tissue homeostasis, and species diversity. Dysregulation of alternative splicing can initiate and drive disease. Aberrant alternative splicing has been shown to promote the "hallmarks of cancer" in both hematological and solid cancers. Of interest, recent work has focused on the role of alternative splicing in prostate cancer and prostate cancer health disparities. We will provide a review of prostate cancer health disparities involving the African American population, alternative RNA splicing, and alternative splicing in prostate cancer. Lastly, we will summarize our work on differential alternative splicing in prostate cancer disparities and its implications for disparate health outcomes and therapeutic targets.


Assuntos
Processamento Alternativo , Resistência a Medicamentos , Disparidades nos Níveis de Saúde , Neoplasias da Próstata , Afro-Americanos/estatística & dados numéricos , Processamento Alternativo/genética , Resistência a Medicamentos/genética , Humanos , Masculino , Neoplasias da Próstata/genética , Neoplasias da Próstata/fisiopatologia
3.
Anticancer Res ; 39(10): 5311-5327, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570425

RESUMO

BACKGROUND/AIM: MiR-221, often described both as an oncogenic microRNA and as a tumour suppressor, targets mRNAs involved in carcinogenesis. While other oncogenic microRNAs showed correlations with prostate cancer cell lines' aggressiveness, miR-221 showed an unusual overexpression in PC3. MATERIALS AND METHODS: CRISPR was used to delete miR-221 from PC3 cells. Analysing the characteristics of PC3miR-221del cells, a reduced growth rate and expression of cell-cycle genes was observed. In global gene expression/ontology analysis of PC3miR-221del cells, cell-cell and cell-substrate adhesion pathways were found to be greatly affected. In addition, reduced levels of adhesion, invasion and motility for PC3miR-221del cells, a change in F-actin localisation and a reduction of EMT markers were observed. RESULTS: The tumour suppressor gene, DIRAS3, was a predicted target of miR-221. In PC3miR-221del cells DIRAS3 was up-regulated at the gene and protein level. Ectopic expression of DIRAS3 in PC3wt cells recapitulated the cellular morphology changes seen in PC3miR-221del cells. DIRAS3 3'UTR was more stable in PC3miR-221del cells, as measured by semi-quantitative PCR and luciferase fusion reporter assays. CONCLUSION: MiR-221 promotes aggressiveness of PC3 cells by down-regulating DIRAS3, and promoting epithelial-to-mesenchymal transition.


Assuntos
Adesão Celular/genética , Movimento Celular/genética , Proliferação de Células/genética , MicroRNAs/genética , Deleção de Sequência/genética , Regiões 3' não Traduzidas/genética , Ciclo Celular/genética , Linhagem Celular Tumoral , Regulação para Baixo/genética , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Masculino , Oncogenes/genética , Células PC-3 , Neoplasias da Próstata/genética , Regulação para Cima/genética , Proteínas rho de Ligação ao GTP/genética
4.
Adv Exp Med Biol ; 1164: 207-224, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31576551

RESUMO

Prostate cancers have a justified reputation as one of the most heterogeneous human tumours. Indeed, there are some who consider that advanced and castration-resistant prostate cancers are incurable, as a direct result of this heterogeneity. However, tumour heterogeneity can be defined in different ways. To a clinician, prostate cancer is a number of different diseases, the treatments for which remain equally heterogeneous and uncertain. To the pathologist, the histopathological appearances of the tumours are notoriously heterogeneous. Indeed, the genius of Donald Gleason in the 1960s was to devise a classification system designed to take into account the heterogeneity of the tumours both individually and in the whole prostate context. To the cell biologist, a prostate tumour consists of multiple epithelial cell types, inter-mingled with various fibroblasts, neuroendocrine cells, endothelial cells, macrophages and lymphocytes, all of which interact to influence treatment responses in a patient-specific manner. Finally, genetic analyses of prostate cancers have been compromised by the variable gene rearrangements and paucity of activating mutations observed, even in large numbers of patient tumours with consistent clinical diagnoses and/or outcomes. Research into familial susceptibility has even generated the least tractable outcome of such studies: the genetic loci are of low penetrance and are of course heterogeneous. By fractionating the tumour (and patient-matched non-malignant tissues) heterogeneity can be resolved, revealing homogeneous markers of patient outcomes.


Assuntos
Células Endoteliais , Neoplasias da Próstata , Células Endoteliais/citologia , Heterogeneidade Genética , Humanos , Masculino , Mutação , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Neoplasias da Próstata/terapia
5.
Cancer Immunol Immunother ; 68(10): 1621-1633, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31549213

RESUMO

Defects in DNA damage repair caused by mutations in BRCA1/2, ATM or other genes have been shown to play an important role in the development and progression of prostate cancer. The influence of such mutations on anti-tumor immunity in prostate cancer, however, is largely unknown. To better understand the correlation between BRCA1/2 mutations and the immune phenotype in prostate cancer, we characterized the immune infiltrate of eight BRCA2-mutated tumors in comparison with eight BRCA1/2 wild-type patients by T-cell receptor sequencing and immunohistochemistry for CD45, CD4, CD8, FOXP3, and CD163. In addition, we analyzed seven prostate cancer biopsies that were either BRCA2 or ATM-mutated in comparison with wild-type tumors. Whereas in BRCA1/2 wild-type tumors, immune cells were found predominantly extratumorally, most BRCA2-mutated tumors including one biopsy showed a significantly increased intratumoral immune cell infiltration. The ratio of intratumoral to extratumoral immune cells was considerably higher in BRCA2-mutated tumors for all markers and reached statistical significance for CD4 (p = 0.007), CD8 (p = 0.006), and FOXP3 (p = 0.001). However, the intratumoral CD8 to FOXP3 ratio showed a trend to be lower in BRCA2-mutated tumors suggesting a more suppressed tumor immune microenvironment. Our findings provide a rationale for the future use of immune oncological approaches in BRCA2-mutated prostate cancer and may encourage efforts to target immunosuppressive T-cell populations to prime tumors for immunotherapy.


Assuntos
Genes BRCA2 , Mutação , Neoplasias da Próstata/imunologia , Antígenos CD8/análise , Fatores de Transcrição Forkhead/análise , Humanos , Masculino , Fenótipo , Neoplasias da Próstata/genética , Linfócitos T/imunologia , Microambiente Tumoral
6.
Med Oncol ; 36(11): 92, 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31560094

RESUMO

Although MYC proto-oncogene (C-MYC) amplification has been consistently reported to be a potential marker for prostate cancer (PCa) progression and prognosis, the clinicopathological and prognostic significance of C-MYC protein expression remains controversial. Overexpression of SOX4 has been shown to play important roles in multiple cancers including PCa. However, the link between these two critical genetic aberrations is unclear. In the current study, we showed that C-MYC was overexpressed in 16.2% (17/105) of Chinese patients with localized PCa. Overexpression of C-MYC was significantly associated with high Gleason scores (P = 0.012) and high Ki67 labeling index (P = 0.005). C-MYC overexpression was correlated with cancer-related mortality and suggested to be an unfavorable prognostic factor in Chinese PCa patients (P = 0.018). Overexpression of C-MYC is associated with SOX4 overexpression in PCa tissues. Notably, SOX4 is a direct target gene of C-MYC; C-MYC activates SOX4 expression via binding to its promoter. In addition, Co-IP analysis demonstrated a physical interaction between C-MYC and SOX4 protein in PCa cells. Clinically, C-MYC+/SOX4+ characterized poor prognosis in a subset of PCa patients. In total, C-MYC overexpression may contribute to PCa progression by activating SOX4. Our findings highlight an important role of C-MYC/SOX4 in PCa progression in a subset of PCa patients.


Assuntos
Neoplasias da Próstata/metabolismo , Proteínas Proto-Oncogênicas c-myc/biossíntese , Fatores de Transcrição SOXC/biossíntese , Idoso , Linhagem Celular Tumoral , Células HEK293 , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Neoplasias de Próstata Resistentes à Castração/genética , Neoplasias de Próstata Resistentes à Castração/metabolismo , Neoplasias de Próstata Resistentes à Castração/patologia , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , Fatores de Transcrição SOXC/genética , Fatores de Transcrição SOXC/metabolismo , Análise Serial de Tecidos
7.
Gene ; 721: 144102, 2019 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-31499125

RESUMO

Advances in DNA sequencing technologies enable researchers to integrate various biological datasets in order to reveal hidden relations at the molecular level. In this study, we present a two-tiered combinatorial structure (TTCS) to integrate gene co-expression networks (GCNs) that are inferred from microarray gene expression, RNA-Seq and miRNA-target gene data. In the initial phase of TTCS, we derive GCNs by using gene network inference (GNI) algorithms for each dataset. In the first and second integration phases, we use straightforward methods: intersection, union and simple majority voting to combine GCNs. We use overlap, topological and biological analyses in performance evaluation and investigate the integration effects of GCNs separately for all phases. Our results prove that the first integration phase has limited contribution on performance. However, combining the biological datasets in the second phase significantly enhances the overlap and topological performance analyses.


Assuntos
Bases de Dados de Ácidos Nucleicos , Regulação Neoplásica da Expressão Gênica , Neoplasias da Próstata , Perfilação da Expressão Gênica , Humanos , Masculino , Análise de Sequência com Séries de Oligonucleotídeos , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia
8.
Pol J Pathol ; 70(2): 127-133, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31556563

RESUMO

We tested the association between HOXB13 G84E (rs138213197) germline mutation and PC risk in Polish men. DNA from 103 consecutive, newly diagnosed patients hospitalised because of PC and DNA from 103 men: volunteers, healthy at the time of the study. The G84E mutation was genotyped using Sanger sequencing. The HOXB13 G84E germline mutation was detected in 2.9% of PC men (3/103) and not detected in any healthy man. Two mutation carriers originated from two of 25 families fulfilling hereditary prostate cancer criteria (HPC) and one mutation carrier from one family among 78 families without HPC (PC frequency: 8% vs. 1.3%, OR = 6.70, p = 0.13). In two of three mutation carriers, disease was detected above 60 years of age. There was a trend for a lower probability of 5-year survival in patients with G84E than in patients without it (66.7% vs. 94.0%, p = 0.08). The HOXB13 G84E germline mutation is associated with increased prostate cancer risk in Polish men, with hereditary form of the disease, and probably with older age at PC onset (> 60 years of age) and shorter survival. However, it is not associated with PSA level, or PC stage or grade at the time of diagnosis.


Assuntos
Mutação em Linhagem Germinativa , Proteínas de Homeodomínio/genética , Neoplasias da Próstata/genética , Idoso , Estudos de Casos e Controles , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Polônia , Antígeno Prostático Específico/sangue , Fatores de Risco
9.
Oncol Rep ; 42(4): 1307-1318, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31364741

RESUMO

Hypoxia is a tumorigenesis­related microenvironment change which usually occurs in the earliest stage of prostate cancer (PCa) development. Accumulating evidence has demonstrated that hypoxia/hypoxia­inducing factor (HIF) is involved in the induction of epithelial­mesenchymal transition (EMT) and increased metastatic potential in PCa. However, the mechanism by which hypoxia/HIF regulates EMT remains unclear. In the present study, we demonstrated the molecular mechanisms of hypoxia­induced EMT in PCa, focusing on HIF­1α/Forkhead box M1 (FoxM1) signaling pathway. PCa PC3 and DU145 cell lines were used as the model system in vitro. Our data revealed that hypoxia induced EMT in PCa cells. Bioinformatics analysis identified the possible association between HIF­1α and FoxM1. Additionally, FoxM1 was significantly associated with PCa development and Gleason scores of PCa. Exposure to hypoxia resulted in the increased expression of HIF­1α and FoxM1. Genetic knockdown FoxM1 abolished hypoxia­induced EMT in PCa, while exogenous overexpression of FoxM1 facilitated hypoxia­induced EMT. Furthermore, the increase of FoxM1 during hypoxia was due to the transcriptional regulation on the FoxM1 promoter by HIF­1α. We also confirmed the binding site of HIF­1α on the FoxM1 promoter by different lengths promoter sequences. These findings provide new insights into how EMT is regulated in PCa under hypoxic stress. It is worthwhile to investigate in future that inhibition of FoxM1 as a potential target may be an effective therapeutic strategy against PCa.


Assuntos
Proteína Forkhead Box M1/genética , Proteína Forkhead Box M1/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Sequência de Bases , Sítios de Ligação , Hipóxia Celular/fisiologia , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal , Humanos , Masculino , Células PC-3 , Regiões Promotoras Genéticas , Neoplasias da Próstata/patologia , Transcrição Genética , Regulação para Cima
10.
Anticancer Res ; 39(8): 4171-4177, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366502

RESUMO

BACKGROUND/AIM: Identification of prostatic stem cells in primary prostate tissue sections, organ cultures of prostate and cell lines requires a range of techniques that allows characterization of stem cells for their potential use in the treatment of patients. Isolated cells usually round-up and develop changes in shape, size and cellular characteristics. The aim of this study was to provide a range of methods for identifying prostatic stem cells and characterizing them with regard to ultrastructure, nuclear morphology, cytoplasmic organelles, and/or expression stem cell marker CD133. MATERIALS AND METHODS: Prostate biopsy and prostatectomy specimens were used for studying prostatic stem cells and their known marker CD133 in tissue sections by light and/or electron microscopy. Inverted capsule embedding was used to study archival metastatic prostate in pelvic nodes and Du145 cell line in a monolayer culture. RESULTS: Staining for CD133 positively identified stem cells that were found in benign prostatic hyperplasia, benign prostate, and prostate cancer cells. Paraffin embedded sections showed a single type of stem cells, whereas methylene blue-stained Epon sections showed both light and dark stem cells. Electron microscopy showed that both basal and stem cells were closely associated with the basement membrane (basal lamina). Stem cells had smooth plasma and nuclear membranes, a prominent nucleolus, small mitochondria, and few ribosomes. Du145 cells were separated by intercellular spaces in monolayer culture. CONCLUSION: The inverted capsule embedding method allowed the study of metastasized prostate cancer in pelvic lymph nodes. Our approach enabled the assessment of stem cells in tissue sections by light and electron microscopy.


Assuntos
Antígeno AC133/genética , Membrana Basal/ultraestrutura , Hiperplasia Prostática/genética , Neoplasias da Próstata/genética , Membrana Basal/patologia , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Masculino , Microscopia Eletrônica , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Células-Tronco Neoplásicas/ultraestrutura , Próstata/metabolismo , Próstata/patologia , Próstata/ultraestrutura , Hiperplasia Prostática/metabolismo , Hiperplasia Prostática/patologia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/ultraestrutura
11.
Int Braz J Urol ; 45(5): 916-924, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31268639

RESUMO

OBJECTIVE: This study aims to investigate the association of filamin A with the function and morphology of prostate cancer (PCa) cells, and explore the role of filamin A in the development of PCa, in order to analyze its significance in the evolvement of PCa. MATERIALS AND METHODS: A stably transfected cell line, in which filamin A expression was suppressed by RNA interference, was first established. Then, the effects of the suppression of filamin A gene expression on the biological characteristics of human PCa LNCaP cells were observed through cell morphology, in vitro cell growth curve, soft agar cloning assay, and scratch test. RESULTS: A cell line model with a low expression of filamin A was successfully constructed on the basis of LNCaP cells. The morphology of cells transfected with plasmid pSilencer-filamin A was the following: Cells were loosely arranged, had less connection with each other, had fewer tentacles, and presented a fibrous look. The growth rate of LNCap cells was faster than cells transfected with plasmid pSilencer-filamin A (P<0.05). The clones of LNCap cells in the soft agar cloning assay was significantly fewer than that of cells stably transfected with plasmid pSilencer-filamin A (P<0.05). Cells stably transfected with plasmid pSilencer-filamin A presented with a stronger healing and migration ability compared to LNCap cells (healing rate was 32.2% and 12.1%, respectively; P<0.05). CONCLUSION: The expression of the filamin A gene inhibited the malignant development of LNCap cells. Therefore, the filamin A gene may be a tumor suppressor gene.


Assuntos
Filaminas/análise , Filaminas/fisiologia , Neoplasias da Próstata/patologia , Western Blotting , Linhagem Celular Tumoral , Proliferação de Células , Células Cultivadas , Colorimetria/métodos , Filaminas/genética , Formazans , Humanos , Masculino , Plasmídeos , Neoplasias da Próstata/genética , Sais de Tetrazólio , Fatores de Tempo , Transfecção/métodos , Cicatrização/fisiologia
13.
Anticancer Res ; 39(7): 3719-3725, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31262898

RESUMO

BACKGROUND: Hormone therapy and chemotherapy are not effective for castrate-resistant prostate cancer, thus development of novel treatment strategies is required. Gene therapy involving transient high-copy transfection of interleukin (IL)-24 with an adenoviral vector can exert antitumor activity; however, the effects of stable IL-24 transfection are not fully understood. The aim of this study was to investigate the effects of IL-24 overexpression in prostate cancer cells, in vitro. MATERIALS AND METHODS: DU145 cells were transfected the IL-24 gene using a retroviral vector. Apoptosis induction was investigated by the cell death detection ELISA, and the gene expression was analyzed by real time RT-PCR. RESULTS: IL-24 transduction suppressed the growth of prostate cancer and induced tumor cell apoptosis. In addition, up-regulation of epithelial markers and down-regulation of mesenchymal markers were noted, suggesting that tumor aggressiveness was reduced. CONCLUSION: Introduction of IL-24 displays antitumor activity both by induction of apoptosis and regulation of anchorage dependence.


Assuntos
Interleucinas/genética , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Apoptose , Proliferação de Células , Humanos , Masculino , Transdução Genética
14.
DNA Cell Biol ; 38(8): 840-848, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31314587

RESUMO

microRNAs are a class of noncoding RNAs that play important roles in cancer progression. microRNA-183-3p (miR-183-3p) is a novel microRNA that is dysregulated in many kinds of cancers. Our previous studies found high expression and oncologic role of high-mobility group nucleosome binding domain 5 (HMGN5) in prostate cancer. In this study, we found that miR-183-3p was downregulated in prostate cancer cells and primary tissues compared with normal controls. In addition, miR-183-3p expression was negatively correlated with HMGN5 expression. On the basis of bioinformatics predication and quantitative polymerase chain reaction and Western blot verification, it is demonstrated that miR-183-3p regulated HMGN5 expression. Luciferase reporter assay confirmed that miR-183-3p directly targeted the 3'-untranslated region of HMGN5. Interestingly, cell proliferation and migration inhibition and apoptosis induction were also observed in miR-183-3p transfected human prostate cancer VCap and C4-2 cells. Moreover, overexpression of HMGN5 significantly reversed the inhibitory effect on cell proliferation and migration and promoted effect on cell apoptosis by miR-183-3p. Our data suggest that dysfunction of miR-183-3p-HMGN5 axis plays an oncogenic role and can be a therapeutic target for prostate cancer.


Assuntos
Proteínas HMGN/genética , MicroRNAs/genética , Neoplasias da Próstata/genética , Transativadores/genética , Regiões 3' não Traduzidas , Idoso , Apoptose/genética , Estudos de Casos e Controles , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Proteínas HMGN/metabolismo , Humanos , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Neoplasias da Próstata/patologia , Transativadores/metabolismo
15.
Zhonghua Yi Xue Za Zhi ; 99(26): 2042-2046, 2019 Jul 09.
Artigo em Chinês | MEDLINE | ID: mdl-31315374

RESUMO

Objective: To investigate the regulation of long-chain non-coding RNA-AC024560.2 transfection on the expression of miR-30a-5p and its effect on proliferation and invasion of prostate cancer cells. Methods: qRT-PCR was used to detect the expression of AC024560.2 in 16 prostate cancer tissues and adjacent normal tissues, prostate cancer cell lines and normal prostate epithelial cells. The cells with the lowest expression amount were transfected, and the prostate cancer cells were divided into control group (transfected with negative control plasmid) and experimental group (transfected with plasmid carrying AC024560.2). Bioinformatics predicted possible target genes for AC024560.2. qRT-PCR was used to detect the expression of AC024560.2 and target genes in the transfected cells. Western blot was used to detect the expression of downstream target proteins. Cell proliferation and invasion were analyzed by MTS assay and Transwell invasion assay. Results: The expression levels of AC024560.2 in prostate cancer tissues and adjacent tissues were 1.95±0.22 and 3.87±0.23, respectively (t=6.09, P<0.01). Compared with normal prostate epithelial cells, the expression of AC024560.2 in prostate cancer cell lines was significantly decreased (P<0.05), and the most significant decrease was observed in C4-2B cell lines (P<0.01). Bioinformatics predictions showed that AC024560.2 bond to miR-30a-5p, and miR-30a-5p bond to SIRT1 mRNA. The expression of AC024560.2 in the experimental group increased significantly (P<0.01), the expression of miR-30a-5p decreased significantly (P<0.01), and the expression of SIRT1 mRNA and protein increased significantly (P<0.01). After transfection with AC024560.2, the cell proliferation ability of the experimental group was significantly decreased from day 2 (P<0.05). The invasive numbers of C4-2B cells in the control group and the experimental group were 130.90±14.54 and 43.77±10.01, respectively (t=4.94, P<0.01). Conclusions: AC024560.2 is lowly expressed in human prostate cancer, and may inhibit the proliferation and invasion of prostate cancer cells by regulating the expression of miR-30a-5p and SIRT1 genes. AC024560.2 may be a potential target for the treatment of prostate cancer.


Assuntos
Neoplasias da Próstata , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , MicroRNAs , Neoplasias da Próstata/genética , RNA Longo não Codificante
16.
J Cancer Res Clin Oncol ; 145(8): 1939-1948, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31263949

RESUMO

OBJECTIVE: Some studies have shown that the methylation status of the GSTP1 gene promoter is related to the incidence of prostate cancer, but this finding is still controversial. The aim of this study was to evaluate the association between glutathione-S-transferase p1 (GSTP1) promoter methylation and the incidence of prostate cancer. METHODS: The Medline, Embase, Web of Science, and Cochrane CENTRAL databases were searched from their inception to February 22, 2019. According to the inclusion criteria, studies of the association between the methylation status of the GSTP1 gene promoter and prostate cancer were included. The difference in the incidence of GSTP1 promoter methylation in tissues, blood, or urine between patients with prostate cancer and those without prostate cancer were compared, and the results were expressed as the odds ratio (OR) and 95% confidence interval (CI). The pooled OR of each study was estimated using a fixed-effects model or a random-effects model to generate forest plots. RESULTS: Ultimately, 15 studies (1540 samples) were included. The estimated effect from our meta-analysis showed that the incidence of GSTP1 promoter methylation was higher in patients with prostate cancer than in those without prostate cancer (OR 18.58, 95% CI 9.60-35.95, P = 0.000). GSTP1 promoter methylation was highly correlated with the incidence of prostate cancer. CONCLUSIONS: Methylation of the GSTP1 promoter may increase the risk of prostate cancer. This study may provide a strategic direction for prostate cancer research. Pending validation of these findings, the methylation of the GSTP1 promoter may be a potential biomarker to diagnose prostate cancer.


Assuntos
Biomarcadores Tumorais/genética , Metilação de DNA/fisiologia , Glutationa S-Transferase pi/genética , Regiões Promotoras Genéticas , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/epidemiologia , Humanos , Incidência , Masculino , Neoplasias da Próstata/genética
17.
Medicine (Baltimore) ; 98(29): e16193, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31335671

RESUMO

MicroRNA-191 (miR-191) has been identified as being upregulated in several types of cancers, and plays the role of oncogene. The expression of miR-191 has been found to be upregulated in prostate cancer tissues as well as cell lines. In this study, we analyzed the correlation of miR-191 expression with clinicopathologic factors and prognosis in prostate cancer.Prostate cancer tissue samples and adjacent normal prostate tissue samples were collected from 146 patients who underwent laparoscopic radical prostatectomy between April 2013 and March 2018. Student two-tailed t-test was used for comparisons of 2 independent groups. The relationships between miR-191 expression and different clinicopathological characteristics were evaluated using the Chi-squared test. Kaplan-Meier survival plots and log-rank tests were used to assess the differences in overall survival of the different subgroups of prostate cancer patients.miR-191 expression was significantly higher in prostate cancer tissues compared with normal adjacent prostate tissues (P < .001). miR-191 expression was observed to be significantly correlated with Gleason score (P < .001), pelvic lymph node metastasis (P = .006), bone metastases (P < .001), and T stage (P = .005). Kaplan-Meier analysis showed that patients with higher levels of miR-191 had significantly poorer survival than those with lower expression of this miRNA in prostate cancer patients (log rank test, P = .011). Multivariate analysis revealed that miR-191 expression (hazard ratio [HR] = 2.311, 95% confidence interval, [CI]: 1.666-9.006; P = .027) was independently associated with the overall survival of prostate cancer patients.Our results demonstrated that miR-191 might serve as an independent prognostic indicator for prostate cancer patients.


Assuntos
MicroRNAs/genética , Prostatectomia , Neoplasias da Próstata , Idoso , Biomarcadores Tumorais/genética , Neoplasias Ósseas/patologia , Neoplasias Ósseas/secundário , China , Regulação Neoplásica da Expressão Gênica , Humanos , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Prognóstico , Prostatectomia/métodos , Prostatectomia/mortalidade , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Análise de Sobrevida , Regulação para Cima/genética
18.
Medicine (Baltimore) ; 98(30): e16534, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31348270

RESUMO

BACKGROUND: High-grade prostate cancer (PCa) has a poor prognosis, and up to 15% of patients worldwide experience lymph node invasion (LNI). To further improve the prediction lymph node invasion in prostate cancer, we adopted risk scores of the genes expression based on the nomogram in guidelines. METHODS: We analyzed clinical data from 320 PCa patients from the Cancer Genome Atlas database. Weighted gene coexpression network analysis was used to identify the genes that were significantly associated with LNI in PCa (n = 390). Analyses using the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases were performed to identify the activated signaling pathways. Univariate and multivariate logistic regression analyses were performed to identify the independent risk factors for the presence of LNI. RESULTS: We found that patients with actual LNI and predicted LNI had the worst survival outcomes. The 7 most significant genes (CTNNAL1, ENSA, MAP6D1, MBD4, PRCC, SF3B2, TREML1) were selected for further analysis. Pathways in the cell cycle, DNA replication, oocyte meiosis, and 9 other pathways were dramatically activated during LNI in PCa. Multivariate analyses identified that the risk score (odds ratio [OR] = 1.05 for 1% increase, 95% confidence interval [CI]: 1.04-1.07, P < .001), serum PSA level, clinical stage, primary biopsy Gleason grade (OR = 2.52 for a grade increase, 95% CI: 1.27-5.22, P = .096), and secondary biopsy Gleason grade were independent predictors of LNI. A nomogram built using these predictive variables showed good calibration and a net clinical benefit, with an area under the curve (AUC) value of 90.2%. CONCLUSIONS: In clinical practice, the application of our nomogram might contribute significantly to the selection of patients who are good candidates for surgery with extended pelvic lymph node dissection.


Assuntos
Biomarcadores Tumorais/genética , Metástase Linfática/genética , Nomogramas , Neoplasias da Próstata/genética , Idoso , Área Sob a Curva , Proteínas de Ciclo Celular/metabolismo , Bases de Dados Genéticas , Endodesoxirribonucleases/metabolismo , Humanos , Modelos Logísticos , Linfonodos/patologia , Masculino , Proteínas Associadas aos Microtúbulos/metabolismo , Pessoa de Meia-Idade , Análise Multivariada , Gradação de Tumores , Proteínas de Neoplasias/metabolismo , Razão de Chances , Peptídeos/metabolismo , Valor Preditivo dos Testes , Neoplasias da Próstata/patologia , Fatores de Processamento de RNA/metabolismo , Receptores Imunológicos/metabolismo , Reprodutibilidade dos Testes , Fatores de Risco , alfa Catenina/metabolismo
19.
Life Sci ; 232: 116626, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31276688

RESUMO

PURPOSE: The aim of this study was to investigate the role of the suppressor of activator protein-1 regulated by interferon (SARI), in the development and progression of prostate cancer. METHODS: Sixty-seven prostate cancer tissue specimens and 20 benign prostatic hyperplasia specimens were used to investigate the correlation between SARI expression and clinicopathologic parameters. Immunohistochemistry was used to detect the SARI and E-cadherin protein expression in the prostate cancer and benign prostatic hyperplasia specimens, and their correlation was established. Quantitative PCR (qPCR) was used to determine the SARI mRNA expression in a normal prostate cell line (RWPE-1) and prostate cancer cell lines (LNCaP and PC3). Western blotting was used to detect the SARI protein expression in the RWPE-1, LNCaP, and PC3 cell lines. RESULTS: SARI protein expression did not correlate with the prostate cancer patients' age or serum Prostate-Specific Antigen value but did show a correlation with the tumor stage of prostate cancer and Gleason score. SARI and E-cadherin expression in the prostate cancer tissue was significantly lower than in the benign prostatic hyperplasia specimens, suggesting a positive correlation between the SARI and E-cadherin expression. SARI mRNA and protein were highly expressed in RWPE-1, the normal prostate cell line, but SARI mRNA and protein expression were reduced in the prostate cancer cell lines, LNCaP and PC3. Significant differences in the expression were found between the prostate cancer cell lines and the normal prostate cell line. CONCLUSION: In this study, high SARI expression was found to be negatively correlated with the development and progression of prostate cancer.


Assuntos
Fatores de Transcrição de Zíper de Leucina Básica/genética , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Neoplasias da Próstata/genética , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo , Idoso , Western Blotting , Caderinas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Progressão da Doença , Regulação Neoplásica da Expressão Gênica/genética , Glicogênio Sintase Quinase 3 beta/metabolismo , Humanos , Imuno-Histoquímica , Interferons/metabolismo , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Fosfatidilinositol 3-Quinases/metabolismo , Próstata/citologia , Próstata/patologia , Hiperplasia Prostática/metabolismo , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Mensageiro/genética , Fator de Transcrição AP-1/metabolismo , beta Catenina/metabolismo
20.
Cell Mol Life Sci ; 76(19): 3723-3744, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31147752

RESUMO

Starting from their role exerted on osteoblast and osteoclast differentiation and activity pathways, microRNAs (miRNAs) have been recently identified as regulators of different processes in bone homeostasis. For this purpose, in a recent review, we highlighted, as deregulated miRNAs could be involved in different bone diseases such as osteoporosis. In addition, recent studies supported the concept that osteoporosis-induced bone alterations might offer a receptive site for cancer cells to form bone metastases, However, to date, no data on specific-shared miRNAs between osteoporosis and bone metastases have been considered and described to clarify the evidence of this link. The main goal of this review is to underline as deregulated miRNAs in osteoporosis may have specific roles in the development of bone metastases. The review showed that several circulating osteoporotic miRNAs could facilitate tumor progression and bone-metastasis formation in several tumor types, i.e., breast cancer, prostate cancer, non-small-cell lung cancer, esophageal squamous cell carcinoma, and multiple myeloma. In detail, serum up-regulation of pro-osteoporotic miRNAs, as well as serum down-regulation of anti-osteoporotic miRNAs are common features of all these tumors and are able to promote bone metastasis. These results are of key importance and could help researcher and clinicians to establish new therapeutic strategies connected with deregulation of circulating miRNAs and able to interfere with pathogenic processes of osteoporosis, tumor progressions, and bone-metastasis formation.


Assuntos
Neoplasias Ósseas/secundário , MicroRNA Circulante/metabolismo , Osteoporose/genética , Animais , Neoplasias Ósseas/complicações , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/secundário , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/secundário , Feminino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , MicroRNAs/metabolismo , Mieloma Múltiplo/genética , Osteoporose/complicações , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia
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