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1.
Medicine (Baltimore) ; 98(33): e16711, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31415363

RESUMO

BACKGROUND: Multiple myeloma (MM) is a clonal plasma cell malignancy associated with hypercalcemia, bone lesions, and renal failure. The prognostic significance of the mutation of miRNAs, one kind of small noncoding RNA molecules that can modulate gene expression, should be confirmed in non-Hodgkin lymphomas (NHL). This study aimed to identify the prognostic value of miRNAs in patients with MM. METHODS: A meta-analysis was performed to estimate the pooled hazard ratios and their corresponding 95% confidence intervals for the associations between levels of miRNA expression (predictive factors) and outcomes in patients with MM. We systematically searched the PubMed, Web of Science, and China National Knowledge Infrastructure databases (final search conducted January 1, 2018) to identify eligible studies. Eligible studies were included by certain inclusion and exclusion criteria, whose quality was assessed by Newcastle-Ottawa Scale. RESULTS: After performing the literature search and review, 10 relevant studies, including 1214 cases, were identified. The results of our meta-analysis revealed that upregulated miR-92a level and downregulated miR-16, miR-25, miR-744, miR-15a, let-7e, and miR-19b expression were associated with poor prognosis in MM. CONCLUSIONS: This study identified miRNAs could serve as potential prognostic biomarkers in MM. Given the limited research available, the clinical application of these findings has yet to be verified.


Assuntos
MicroRNAs/metabolismo , Mieloma Múltiplo/genética , Biomarcadores Tumorais/metabolismo , Regulação para Baixo , Feminino , Expressão Gênica , Humanos , Masculino , Mutação , Prognóstico , Modelos de Riscos Proporcionais , Regulação para Cima
2.
Medicine (Baltimore) ; 98(33): e16807, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31415393

RESUMO

BACKGROUND: Sepsis is a serious clinical condition with a poor prognosis, despite improvements in diagnosis and treatment.Therefore, novel biomarkers are necessary that can help with estimating prognosis and improving clinical outcomes of patients with sepsis. METHODS: The gene expression profiles GSE54514 and GSE63042 were downloaded from the GEO database. DEGs were screened by t test after logarithmization of raw data; then, the common DEGs between the 2 gene expression profiles were identified by up-regulation and down-regulation intersection. The DEGs were analyzed using bioinformatics, and a protein-protein interaction (PPI) survival network was constructed using STRING. Survival curves were constructed to explore the relationship between core genes and the prognosis of sepsis patients based on GSE54514 data. RESULTS: A total of 688 common DEGs were identified between survivors and non-survivors of sepsis, and 96 genes were involved in survival networks. The crucial genes Signal transducer and activator of transcription 5A (STAT5A), CCAAT/enhancer-binding protein beta (CEBPB), Myc proto-oncogene protein (MYC), and REL-associated protein (RELA) were identified and showed increased expression in sepsis survivors. These crucial genes had a positive correlation with patients' survival time according to the survival analysis. CONCLUSIONS: Our findings indicate that the genes STAT5A, CEBPB, MYC, and RELA may be important in predicting the prognosis of sepsis patients.


Assuntos
Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Fator de Transcrição STAT5/metabolismo , Sepse/genética , Sepse/mortalidade , Fator de Transcrição RelA/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Idoso , Idoso de 80 Anos ou mais , Biologia Computacional , Bases de Dados Genéticas , Regulação para Baixo , Feminino , Marcadores Genéticos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Mapas de Interação de Proteínas , Fatores de Tempo , Transcriptoma , Regulação para Cima
3.
Braz J Med Biol Res ; 52(8): e8522, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31365696

RESUMO

Pancreaticobiliary maljunction (PBM) is associated with high risk of epithelial atypical growth and malignant transformation of the bile duct or gallbladder. However, overall changes in genetic expression have not been examined in children with PBM. Genome-wide expression was analyzed using peripheral blood samples from 10 children with PBM and 15 pediatric controls. Differentially expressed genes (DEGs) were identified using microarray. Bioinformatics analysis was conducted using Gene Ontology and KEGG analyses. The top 5 in the up-regulated genes in PBM were verified with qRT-PCR. Receiver operator characteristic curve analysis was conducted to evaluate the predictive accuracy of selected genes for PBM. The microarray experiments identified a total of 876 DEGs in PBM, among which 530 were up-regulated and the remaining 346 were down-regulated. Verification of the top 5 up-regulated genes (TYMS, MYBPC1, FUT1, XAGE2, and GREB1L) by qRT-PCR confirmed the up-regulation of MYBPC1 and FUT1. Receiver operating characteristic curve analysis suggested that FUT1 and MYBPC1 up-regulation could be used to predict PBM, with the area under the curve of 0.873 (95%CI=0.735-1.000) and 0.960 (95%CI=0.891-1.000), respectively. FUT1 and MYBPC1 were up-regulated in children with PBM, and could be used as potential biomarkers for PBM.


Assuntos
Ductos Biliares/anormalidades , Proteínas de Transporte/genética , Fucosiltransferases/genética , Perfilação da Expressão Gênica , Ductos Pancreáticos/anormalidades , Regulação para Cima/genética , Neoplasias dos Ductos Biliares/etiologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Dilatação Patológica/complicações , Dilatação Patológica/congênito , Feminino , Neoplasias da Vesícula Biliar/etiologia , Humanos , Lactente , Masculino , Análise em Microsséries
4.
Gene ; 716: 144031, 2019 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-31377314

RESUMO

Circular RNAs (circRNAs), a novel class of widespread and diverse endogenous RNAs, have been identified as critical regulators of various cancers, including hepatocellular carcinoma (HCC). However, the specific roles of circRNAs in HCC are largely unknown. In this study, we identified a novel circRNA, circ-IGF1R, in HCC tumour tissues and cell lines. Circ-IGF1R levels were found to be significantly upregulated in HCC tissues compared with levels in paired peritumoural tissues. The high expression levels of circ-IGF1R in HCC were associated with tumour size. Moreover, knocking down circ-IGF1R with siRNA significantly attenuated cell proliferation and induced cell apoptosis and cell cycle arrest in vitro. Further investigation revealed that PI3K/AKT signalling pathway activation was involved in the oncogenic functions of circ-IGF1R in HCC. Our study suggests that circ-IGF1R may be a potential target for the prevention and treatment of HCC.


Assuntos
Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , RNA/metabolismo , Apoptose , Carcinoma Hepatocelular/enzimologia , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Ciclo Celular , Linhagem Celular , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Humanos , Neoplasias Hepáticas/enzimologia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Fosfatidilinositol 3-Quinase/antagonistas & inibidores , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Regulação para Cima
5.
Gene ; 716: 144032, 2019 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-31377316

RESUMO

Mitochondrial folate metabolism is central to the generation of nucleotides, fuelling methylation reactions, and redox homeostasis. Uniquely among the reactions of the mitochondrial folate pathway, the key step of the oxidation of 5,10-methylene-tetrahydrofolate (CH2-THF) can be catalysed by two isozymes, MTHFD2 and MTHFD2L. The MTHFD2 enzyme has recently received considerable attention as an oncogenic enzyme upregulated in several tumour types, which is additionally required by cancer cells in vitro and in vivo. However, much less is currently known about MTHFD2L and its expression in cancer. In this study, we examine and compare the expression and regulation of the two mitochondrial MTHFD isozymes in normal human and cancer cells. We found that normal and cancer cells express both enzymes, although MTHFD2 has a much higher baseline expression. Unlike MTHFD2, the MTHFD2L isozyme does not show an association with proliferation and growth factor stimulation. In addition, we did not find evidence of a compensatory increase of MTHFD2L following suppression of its isozyme. This study supports that MTHFD2L is unlikely to have an important function in increased proliferation or cancer. Furthermore, therapeutic strategies aiming to block the mitochondrial folate pathway in cancer should focus on MTHFD2, with MTHFD2L being unlikely to be involved in the development of chemoresistance to targeting of its mitochondrial isozyme.


Assuntos
Aminoidrolases/metabolismo , Metilenotetra-Hidrofolato Desidrogenase (NADP)/metabolismo , Enzimas Multifuncionais/metabolismo , Neoplasias/enzimologia , Aminoidrolases/genética , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Isoenzimas/genética , Isoenzimas/metabolismo , Células MCF-7 , Metilenotetra-Hidrofolato Desidrogenase (NADP)/genética , Enzimas Multifuncionais/genética , Neoplasias/genética , Regulação para Cima
6.
Cell Physiol Biochem ; 53(1): 172-185, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31264811

RESUMO

BACKGROUND/AIMS: MicroRNAs (miRs) are transcribed as stem-loop precursors harboring two different miRs on either side of the structure. Both miRs can modulate levels of cellular transcripts based on sequence complementarity between the miR and the mRNA target. The miR of the current study, miR-675, is encoded in the H19 gene with high expression in fetal/placental tissues but low levels in most adult tissues except for skeletal muscle and articular cartilage. miR-675 has a supportive role in expression of the major collagen component of articular cartilage (COL2A1) but it is unknown which arm contributes to this effect. Objectives: To determine the active arm of miR-675 in human articular chondrocytes. To evaluate effects of overexpression of both arms of miR-675 on MMP1 and MMP13, two enzymes involved in breakdown of COL2A1. To investigate whether abundance of both arms of miR-675 is dynamic. METHODS: miR-arm activity was determined by association with the AGO2 complex using immunoprecipitation with an AGO2 specific antibody. miR overexpression and inhibition was used to identify indirect downstream effects on two targets of the Matrix-Metalloprotease family, MMP1 and MMP13. Data was evaluated by qPCR and enzymatic activity assays. Early passage human articular chondrocytes (up to passage 2) obtained from cartilage from both healthy and osteoarthritis affected tissue were used. To evaluate miR-675 levels in a different model, myotube differentiation was employed. RESULTS: We show that both arms of miR-675 have opposing effects on MMP1 and MMP13; however only one arm, miR-675-3' is active in human articular chondrocytes. We demonstrate that during myotube differentiation, high expression of both arms of miR-675 is observed as well as an increase in expression of MMP1. CONCLUSION: We show that both arms of miR-675 result in opposing effects on two downstream molecules MMP1 and MMP13. We propose that miR abundance may arise as response to direct target transcript levels and are thus dynamic to meet the requirements of the cellular environment.


Assuntos
Condrócitos/metabolismo , Regulação da Expressão Gênica , Metaloproteinase 13 da Matriz/genética , Metaloproteinase 1 da Matriz/genética , MicroRNAs/genética , Osteoartrite/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Cartilagem Articular/citologia , Cartilagem Articular/metabolismo , Cartilagem Articular/patologia , Células Cultivadas , Criança , Condrócitos/citologia , Condrócitos/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite/patologia , Regulação para Cima , Adulto Jovem
7.
Zhonghua Xue Ye Xue Za Zhi ; 40(6): 490-496, 2019 Jun 14.
Artigo em Chinês | MEDLINE | ID: mdl-31340622

RESUMO

Objective: To investigate the proteins expression difference after upregulation of human CD99 in Hodgkin Lymphoma cell line, L428 cell, and verify the function of differential proteins. Methods: The differential proteins were detected by two-dimensional fluorescence difference gel electrophoresis and mass spectrometry analysis, cluster analysis was done by GOfact. Results: There were 38 proteins screened out, of which 21 proteins were positively associated with CD99, while 17 proteins were negative. Among the 38 proteins, 32 proteins participated in biological process, and 35 proteins were involved in the composition and construction. And 28 proteins participated in multifaceted biological activities including antioxidation, protein binding, catalytic activity, regulation of enzyme, signal transduction, molecular structure, regulation of translation and ion transport. Conclusions: The changes of the differential proteins, correlated with cytoskeleton, cell differentiation, signal pathway and regulating gene expression, are closely relevant to the translation between Hodgkin/Reed-Sternberg and B lymphocyte cell.


Assuntos
Doença de Hodgkin , Antígeno 12E7 , Linhagem Celular Tumoral , Humanos , Proteômica , Regulação para Cima
8.
Gene ; 715: 143995, 2019 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-31336140

RESUMO

Diabetic cardiomyopathy (DCM) refers to the myocardial dysfunction in the absence of coronary artery disease and hypertension. Recently, the role of microRNAs (miRs) in gene expression regulation has attracted much more attention. Studies have shown that the PI3K/Akt signaling pathway is involved in the growth, metabolism and apoptosis of myocardial cells. Therefore, this study aimed to explore the regulatory role of miR-203 in myocardial fibrosis in mice with DCM via involvement of the PI3K/Akt signaling pathway. Firstly, mouse model of diabetes mellitus (DM) was established and injected with agomir, antagomir or IGF-1 (PI3K/Akt signaling pathway activator) for investigating the role of miR-203 in PIK3CA and the PI3K/Akt signaling pathway. PIK3CA was identified as a target gene of miR-203, and overexpressed miR-203 inhibited the activation of PI3K/Akt signaling pathway. The obtained results indicated that up-regulation of miR-203 reduced myocardial hypertrophy, myocardial fibrosis, myocardial apoptosis, and levels of PIK3CA, PI3K, Akt, CoI I, CoI III, ANP, MDA and ROS in the myocardial tissues, by which DM-induced cardiac dysfunction and pathological changes could be ameliorated. Collectively, our present study highlighted that overexpression of miR-203 may function as a cardioprotective regulator in DCM by targeting PIK3CA via inactivation of PI3K/Akt signaling pathway.


Assuntos
Cardiomiopatias Diabéticas/metabolismo , MicroRNAs/metabolismo , Miocárdio/metabolismo , Estresse Oxidativo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Regulação para Cima , Animais , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Cardiomiopatias Diabéticas/patologia , Fibrose , Camundongos , Miocárdio/patologia
9.
Anticancer Res ; 39(7): 3493-3498, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31262873

RESUMO

BACKGROUND/AIM: Pancreatic cancer is the most lethal cancer of the digestive system. IL-29 is a new member of the IFNλ family and well-known for its strong antiviral activity. However, its direct effect on pancreatic cancer is still unclear. This study was performed to investigate if IL-29 has any direct effect on Pan-48 pancreatic cancer cells. MATERIALS AND METHODS: Clonogenic survival assay, cell proliferation, and caspase-3 activity kits were used to evaluate the effects of IL-29 on cell survival, proliferation, and apoptosis of Pan-48 pancreatic cancer cells. RT-PCR and IHC were subsequently performed to explore IL-29's potential molecular mechanisms. RESULTS: The percentage of colonies of Pan-48 cells was decreased following the addition of IL-29. This was consistent with a decreased optical density (OD) value of cancer cells. Furthermore, the relative caspase-3 activity in cancer cells was increased after the addition of IL-29, indicating increased apoptosis of cancer cells. The anti-proliferative effect of IL-29 on cancer cells correlated with increased expression of the anti-proliferative molecule p21. The pro-apoptotic effect of IL-29 on cancer cells correlated with an increased expression of the pro-apoptotic molecule Bax. CONCLUSION: IL-29 constrains Pan-48 pancreatic cell growth via up-regulation of p21 and Bax. Our study suggests a potential use of IL-29 in immunotherapy for pancreatic cancer treatment.


Assuntos
Antineoplásicos/farmacologia , Inibidor de Quinase Dependente de Ciclina p21/genética , Interleucinas/farmacologia , Neoplasias Pancreáticas/tratamento farmacológico , Proteína X Associada a bcl-2/genética , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , RNA Mensageiro/metabolismo , Regulação para Cima , Proteína X Associada a bcl-2/metabolismo
10.
Gene ; 714: 143992, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31330234

RESUMO

Increasing studies have demonstrated the important roles of circular RNAs (circRNAs) in human malignancies. Nevertheless, the molecular mechanisms and functions of circRNAs in hepatocellular carcinoma (HCC) are still not fully understood. In the present study, we evaluated circ_0021093 expression in 82 pairs of HCC tissues and 5 cell lines by qRT-PCR. The clinical implications of circ_0021093 were evaluated. In addition, the viability, apoptosis, migration and invasion capacities of different HCC cells were evaluated by gain-/loss-of-function experiments. Target prediction and dual-luciferase reporter experiments were performed to identify the molecular mechanisms of circ_0021093. Upregulation of circ_0021093 was found in HCC tumor samples and cells. Additionally, upregulated circ_0021093 was related to adverse clinical characteristics and an unfavorable prognosis. Furthermore, downregulated circ_0021093 attenuated cell growth, migration and invasion but increased cell apoptosis. By contrast, ectopically expressed circ_0021093 enhanced the abovementioned malignant biological behaviors. For mechanism exploration, circ_0021093 sponges of miR-766-3p were used in HCC cells. In addition, we found that metastasis-associated protein 3 (MTA3) was a direct target of miR-766-3p and that the oncogenic function of circ_0021093 was partly dependent on the miR-766-3p/MTA3 axis according to rescue assays. In conclusion, the circ_0021093/miR-766-3p/MTA3 regulatory axis may be an effective therapeutic target for HCC.


Assuntos
Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , MicroRNAs/genética , Proteínas de Neoplasias/genética , RNA/genética , Apoptose/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Progressão da Doença , Regulação para Baixo/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Células Hep G2 , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Regulação para Cima/genética
11.
Parasit Vectors ; 12(1): 348, 2019 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-31300064

RESUMO

BACKGROUND: In the last decade, resistance to antimonials has become a serious problem due to the emergence of drug-resistant strains. Therefore, understanding the mechanisms used by Leishmania parasites to survive under drug pressure is essential, particularly for species of medical-veterinary importance such as L. amazonensis. METHODS: Here, we used RNA-seq technology to analyse transcriptome profiles and identify global changes in gene expression between antimony-resistant and -sensitive L. amazonensis promastigotes. RESULTS: A total of 723 differentially expressed genes were identified between resistant and sensitive lines. Comparative transcriptomic analysis revealed that genes encoding proteins involved in metabolism (fatty acids) and stress response, as well as those associated with antimony resistance in other Leishmania species, were upregulated in the antimony-resistant line. Most importantly, we observed upregulation of genes encoding autophagy proteins, suggesting that in the presence of trivalent stibogluconate (SbIII) L. amazonensis can activate these genes either as a survival strategy or to induce cell death, as has been observed in other parasites. CONCLUSIONS: This work identified global transcriptomic changes in an in vitro-adapted strain in response to SbIII. Our results provide relevant information to continue understanding the mechanism used by parasites of the subgenus Leishmania (L. amazonensis) to generate an antimony-resistant phenotype.


Assuntos
Gluconato de Antimônio e Sódio/farmacologia , Antiprotozoários/farmacologia , Resistência a Medicamentos/genética , Leishmania/efeitos dos fármacos , Leishmania/genética , Transcriptoma , DNA de Protozoário/genética , Perfilação da Expressão Gênica , Ontologia Genética , Fenótipo , Análise de Sequência de RNA , Regulação para Cima
12.
Vet Immunol Immunopathol ; 213: 109880, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31307669

RESUMO

Haemorrhagic enteritis (HE) is a viral disease affecting intestinal integrity and barrier function in turkey (Meleagris gallopavo) and resulting in a significant economic loss. Sequential Windowed Acquisition of All Theoretical Fragment Ion Mass Spectra (SWATH-MS) was applied to identify crucial proteins involved in HE infection. A total of 938 proteins were identified and used to generate a reference library for SWATH-MS analysis. In total, 523 proteins were reliably quantified, and 64 proteins were found to be differentially expressed, including 49 up-regulated and 15 down-regulated proteins between healthy and HE-affected intestinal mucosa. Functional analysis suggested that these proteins were involved in the following categories of cellular pathways and metabolisms: 1) energy pathways; 2) intestine lipid and amino acid metabolism; 3) oxidative stress; 4) intestinal immune response. Major findings of this study demonstrated that natural HE infection is related to the changes in abundance of several proteins involved in cell-intrinsic immune defense against viral invasion, systemic inflammation, modulation of excessive inflammation, B and T cell development and function and antigen presentation. mRNA quantitative expression demonstrated that most of the proteins involved in innate immunity that were found to be differentially abundant were produced by intestinal mucosa, suggesting its direct involvement in immune defences against HE infection.


Assuntos
Infecções por Adenoviridae/veterinária , Mucosa Intestinal/metabolismo , Proteoma , Siadenovirus , Perus/virologia , Infecções por Adenoviridae/metabolismo , Animais , Regulação para Baixo , Enterite , Feminino , Imunidade Inata , Inflamação , Mucosa Intestinal/virologia , Espectrometria de Massas , Redes e Vias Metabólicas , Proteômica , Regulação para Cima
13.
Medicine (Baltimore) ; 98(27): e16225, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31277135

RESUMO

MicroRNAs (miRNAs) play a great contribution to the development of diabetic nephropathy (DN). The aim of this study was to explore potential miRNAs-genes regulatory network and biomarkers for the pathogenesis of DN using bioinformatics methods.Gene expression profiling data related to DN (GSE1009) was obtained from the Gene Expression Omnibus (GEO) database, and then differentially expressed genes (DEGs) between DN patients and normal individuals were screened using GEO2R, followed by a series of bioinformatics analyses, including identifying key genes, conducting pathway enrichment analysis, predicting and identifying key miRNAs, and establishing regulatory relationships between key miRNAs and their target genes.A total of 600 DEGs associated with DN were identified. An additional 7 key DEGs, including 6 downregulated genes, such as vascular endothelial growth factor α (VEGFA) and COL4A5, and 1 upregulated gene (CCL19), were identified in another dataset (GSE30528) from glomeruli samples. Pathway analysis showed that the down- and upregulated DEGs were enriched in 14 and 6 pathways, respectively, with 7 key genes mainly involved in extracellular matrix-receptor interaction, PI3K/Akt signaling, focal adhesion, and Rap1 signaling. The relationships between miRNAs and target genes were constructed, showing that miR-29 targeted COL4A and VEGFA, miR-200 targeted VEGFA, miR-25 targeted ITGAV, and miR-27 targeted EGFR.MiR-29 and miR-200 may play important roles in DN. VEGFA and COL4A5 were targeted by miR-29 and VEGFA by miR-200, which may mediate multiple signaling pathways leading to the pathogenesis and development of DN.


Assuntos
Biologia Computacional/métodos , Nefropatias Diabéticas/genética , Perfilação da Expressão Gênica/métodos , MicroRNAs/genética , Regulação para Cima , Redes Reguladoras de Genes , Humanos , Análise em Microsséries
14.
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
15.
Gene ; 712: 143958, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31278963

RESUMO

The Wnt signaling pathway has been identified for its function in carcinogenesis and embryonic development. It is known to play a vital role in the initiation and development of colorectal cancer (CRC). Therefore, it is of great importance for CRC research to illuminate the mechanisms which regulate Wnt pathway activity. Here, we intended to examine the effect of hsa-miR-942 (miR-942) on the Wnt signaling activity, cell cycle progression, and its expression in CRC tissues. RT-qPCR results indicated that miR-942 is significantly upregulated in colorectal cancer. Then, overexpression of miR-942 promoted, whereas its inhibition decreased the Wnt signaling activity, detected by RT-qPCR and Top/Fop flash assay. Inhibition of Wnt signaling by using PNU-74654 or IWP-2 small molecules indicated that miR-942 applies its effect to the ß-catenin degradation complex level. Then, RT-qPCR and dual luciferase assay showed that miR-942 upregulated Wnt signaling through direct targeting of APC, which is a tumor suppressor in Wnt signaling pathway. Furthermore, the western blotting analysis indicated that ß.catenin, as a main member of Wnt signaling pathway is upregulated following the overexpression of miR-942. Finally, miR-942 overexpression resulted in cell cycle progression in SW480 cells. Taken together, our findings established an oncogenic role for miR-942 in CRC and indicated that this miRNA might be a crucial target for CRC therapy.


Assuntos
Neoplasias Colorretais/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Via de Sinalização Wnt , Regiões 3' não Traduzidas , Carcinogênese/genética , Ciclo Celular , Linhagem Celular Tumoral , Neoplasias Colorretais/genética , Biologia Computacional , Ciclina D1/metabolismo , Progressão da Doença , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Luciferases/metabolismo , Masculino , Plasmídeos/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Interferência de RNA , RNA Longo não Codificante/genética , Transdução de Sinais , Regulação para Cima , beta Catenina/metabolismo
16.
Gene ; 712: 143945, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31279712

RESUMO

Reactive oxygen species, generated in all the aerobic organisms, can cause oxidative stress. Excessive ROS may become a source of carcinogen due to DNA damage, lipid peroxidation, cell injury, and cell death. In order to prevent these adverse effects of ROS, antioxidant enzymes have evolved in aerobic organisms. Catalase is a major antioxidant enzyme that breaks down excessive H2O2 and inhibits apoptotic cell death. Here we molecularly characterized catalase from red-lip mullet. The cDNA sequence of LhCAT consists of an ORF of 1545 bp, which encodes a 527 amino acid peptide (~60 kDa). Based on bioinformatics analysis, LhCAT possesses a domain architecture characteristic of catalases, including a catalase proximal active site signature and a catalase proximal heme-ligand signature. It also has heme and NADPH binding sites homologous to previously described catalases. Pairwise alignment with its homologs revealed that LhCAT shares 95.1% identity with Oplegnathus fasciatus catalase and 97.4% similarity with Sparus aurata catalase. An uprooted phylogenetic tree demonstrated that LhCAT resides in a clade with catalases from other teleosts and exhibits a close relationship with Oplegnathus fasciatus catalase. Among twelve tissue types, we observed the highest LhCAT mRNA expression in the liver, followed by blood. Immune challenge by Lactococcus garvieae, or Poly I:C in the blood or spleen resulted in up-regulation at 24 h post injection. We also tested the antioxidant activity of recombinant LhCAT against hydrogen peroxide and found its optimal concentration to be 12.5 µg/mL. Collectively, these data suggested that LhCAT play an important role in antioxidant defense and immune response of red-lip mullet.


Assuntos
Catalase/metabolismo , Proteínas de Peixes/metabolismo , Smegmamorpha , Adjuvantes Imunológicos , Animais , Antioxidantes/metabolismo , Catalase/genética , DNA Complementar/genética , Proteínas de Peixes/genética , Perfilação da Expressão Gênica , Regulação Enzimológica da Expressão Gênica , Heme/química , Peróxido de Hidrogênio/química , Sistema Imunitário , Ligantes , Fígado/enzimologia , Estresse Oxidativo , Filogenia , RNA Mensageiro/metabolismo , Espécies Reativas de Oxigênio , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Regulação para Cima
18.
Nan Fang Yi Ke Da Xue Xue Bao ; 39(7): 810-815, 2019 Jul 30.
Artigo em Chinês | MEDLINE | ID: mdl-31340914

RESUMO

OBJECTIVE: To investigate the role of Cyr61 in angiotensin Ⅱ (AngⅡ)-induced functional changes in HEK293 cells and explore the mechanism. METHODS: Cyr61 knockdown in cultured HEK293T cells was achieved by transfection of the cells with CRISPR/Cas9 KO plasmid. The changes in apoptosis and expression levels of Cyr61 and Bcl-2 in the cells with or without Cyr61 knockdown in response to treatment with 10-7 mol/L AngⅡ for 48 h were analyzed using flow cytometry, qRT-PCR and Western blotting. RESULTS: The cells with Cyr61 knockdown showed significantly decreased expression of Cyr61 protein as compared with the control cells (P < 0.05). AngⅡ treatment for 48 h significantly increased the expression of Cyr61 and lowers the expression of Bcl-2 at both the protein and mRNA levels in HEK293T cells. In HEK293T cells with Cyr61 knockdown, AngⅡ treatment resulted in significantly increased expression of Bcl-2 in HEK293T cells as compared with that of the control group (P < 0.05). AngⅡ treatment caused significantly increased apoptotic rate in HEK293T cells as compared with the cells with Cyr61 knockdown [(26.94 ± 3.73)% vs (3.87 ± 0.83)%, P < 0.05), and the apoptosis rate was significantly lowered to (15.76 ± 1.31)% in HEK293T cells with Cyr61 knockdown following AngⅡ treatment (P < 0.05). CONCLUSIONS: The up-regulation of Cyr61 expression is related with AngⅡ-induced injury in HEK293T cells, and down-regulating Cyr61 expression can effectively protect HEK293T cells against AngⅡ-induced injury.


Assuntos
Angiotensina II , Apoptose , Proteína Rica em Cisteína 61 , Células HEK293 , Humanos , Regulação para Cima
19.
Cancer Invest ; 37(7): 288-292, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31319725

RESUMO

The proportion of anal cancer cases that produce elevated carcinoembryonic antigen (CEA) levels is not well described in the medical literature. In this study, we used electronic health record data from a single urban cancer center to identify patients from 2004-2018 with anal cancer who have also had a pre-initial treatment CEA measurement. We identified 40 patients who met our eligibility criteria. Of those, 11 (27.5%) had an elevated pretreatment CEA. Elevated CEA was not associated with any of the clinical or demographic covariates; however, three out of five patients with a recurrence had an elevated CEA.


Assuntos
Neoplasias do Ânus/metabolismo , Antígeno Carcinoembrionário/sangue , Carcinoma de Células Escamosas/metabolismo , Neoplasias do Ânus/patologia , Carcinoma de Células Escamosas/patologia , Feminino , Humanos , Masculino , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Regulação para Cima
20.
Cancer Invest ; 37(7): 293-298, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31328584

RESUMO

The aim of the study is to analyse the expression of Interleukin-6 receptor in different human gastric tissue and to correlate with the clinicopathological features of the patients. Immunohistochemistry was done against the IL-6R antibody and the Q-score was calculated from the staining pattern. Higher Q-scores were observed in tumour cells than the adjacent normal cells which were statistically significant. We also observed a significant correlation between the expressions of IL-6R and the clinicopathological features These findings suggest that IL-6R may represent as a therapeutic target for gastric carcinoma and serve as a prognostic indicator, as well.


Assuntos
Biomarcadores Tumorais/metabolismo , Receptores de Interleucina-6/metabolismo , Neoplasias Gástricas/metabolismo , Regulação para Cima , Adulto , Idoso , Idoso de 80 Anos ou mais , Membrana Celular/metabolismo , Citoplasma/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico
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