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1.
Artigo em Inglês | MEDLINE | ID: mdl-34672813

RESUMO

Background: Cell division cycle 45 (CDC45) plays an important role in the occurrence and development of numerous carcinomas, but its effect in laryngeal squamous cell carcinoma (LSCC) remains unclear. Materials and Methods: The messenger RNA and protein expression levels of CDC45 in LSCC were evaluated with a t test and the standard mean difference (SMD). The ability of CDC45 expression to distinguish the LSCC was assessed through receiver operating characteristic (ROC) curves. Gene set enrichment analysis (GSEA), protein-protein interaction, public databases, and online tools were used to explore the potential molecular mechanism of CDC45 in LSCC. Results: A high expression of CDC45 was identified in LSCC (SMD = 2.61, 95% confidence interval [1.62-3.61]). Through ROC curves, the expression of CDC45 makes it feasible to distinguish the LSCC group from the non-LSCC counterpart. CDC45 was relevant to the progression-free interval of LSCC patients (log-rank p = 0.03). GSEAs show that CDC45 is related to the cell cycle. CDC45, CDC6, KIF2C, and AURKB were identified as hub genes of LSCC. E2F1 may be the regulatory transcription factor of CDC45. Conclusions: High expression of CDC45 likely demonstrates carcinogenic effects in LSCC, and CDC45 is a potential target in screening and treatment of LSCC.

2.
Math Biosci Eng ; 18(5): 6941-6960, 2021 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-34517565

RESUMO

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers in the world, the detection and prognosis of which are still unsatisfactory. Thus, it is essential to explore the factors that may identify ESCC and evaluate the prognosis of ESCC patients. RESULTS: Both protein and mRNA expression levels of BIRC5 are upregulated in ESCC group rather than non-ESCC group (standardized mean difference > 0). BIRC5 mRNA expression is related to the age, tumor location, lymph node stage and clinical stage of ESCC patients (p < 0.05). BIRC5 expression makes it feasible to distinguish ESCC from non-ESCC (area under the curve > 0.9), and its high expression is related to poor prognosis of ESCC patients (restrictive survival time difference = -0.036, p < 0.05). BIRC5 may play an important role in ESCC by influencing the cell cycle pathway, and CDK1, MAD2L and CDC20 may be the hub genes of this pathway. The transcription factors-MAZ and TFPD1 -are likely to regulate the transcription of BIRC5, which may be one of the factors for the high expression of BIRC5 in ESCC. CONCLUSIONS: The current study shows that upregulation of BIRC5 may have essential clinical value in ESCC, and contributes to the understanding of the pathogenesis of ESCC.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Survivina/genética , Regulação para Cima
3.
Mol Med Rep ; 23(1)2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33179084

RESUMO

Lung cancer is the most prevalent and observed type of cancer in Xuanwei County, Yunnan, South China. Lung cancer in this area is called Xuanwei lung cancer. However, its pathogenesis remains largely unknown. To date, a number of studies have shown that microRNA (miR)­218 functions as a tumor suppressor in multiple types of cancer. However, the role of miR­218 and its regulatory gene network in Xuanwei lung cancer have yet to be investigated. The current study identified that the expression levels of miR­218 in XWLC­05 cells were markedly lower compared with those in immortalized lung epithelial BEAS­2B cells. The present study also demonstrated that overexpression of miR­218 could decrease cell proliferation, invasion, viability and migration in Xuanwei lung cancer cell line XWLC­05 and NSCLC cell line NCI­H157. Additionally, the results revealed that overexpression of miR­218 could induce XWLC­05 and NCI­H157 cell apoptosis by arresting the cell cycle at G2/M phase. Finally, the present study demonstrated that overexpression of miR­218 could lead to a significant increase in phosphatase and tensin homolog (PTEN) and YY1 transcription factor (YY1), and a decrease in B­cell lymphoma 2 (BCL­2) and BMI1 proto­oncogene, polycomb ring finger (BMI­1) at the mRNA and protein level in XWLC­05 and NCI­H157 cell lines. However, we did not observe any remarkable difference in the roles of miR­218 and miR­218­mediated regulation of BCL­2, BMI­1, PTEN and YY1 expression in the progression of Xuanwei lung cancer. In conclusion, miR­218 could simultaneously suppress cell proliferation and tumor invasiveness and induce cell apoptosis by increasing PTEN and YY1 expression, while decreasing BCL­2 and BMI­1 in Xuanwei lung cancer. The results demonstrated that miR­218 might serve a vital role in tumorigenesis and progression of Xuanwei lung cancer and overexpression of miR­218 may be a novel approach for the treatment of Xuanwei lung cancer.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Regulação para Baixo , Neoplasias Pulmonares/genética , MicroRNAs/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Ciclo Celular , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Sobrevivência Celular , China , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/metabolismo , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , Complexo Repressor Polycomb 1/genética , Complexo Repressor Polycomb 1/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Fator de Transcrição YY1/genética , Fator de Transcrição YY1/metabolismo
4.
Bioengineered ; 12(1): 208-224, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33315534

RESUMO

The screening and treatment of laryngeal squamous cell carcinoma (LSCC) still perplexes clinicians, making it necessary to explore new markers. To this end, this research examined the underlying molecular mechanism of LSCC based on high-throughput datasets (n = 249) from multiple databases. It also identified transcription factors (TFs) independently associated with LSCC prognosis. Through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses, differential expression genes of LSCC were deemed relevant to the extracellular matrix and its related structures or pathways, suggesting that the extracellular matrix plays an important role in LSCC. At the same time, several hub genes that may also have important roles in LSCC were identified via protein-protein interaction analysis, including CDC45, TPX2, AURKA, KIF2C, NUF, MUC1, MUC7, MUC4, MUC15, and MUC21. Eight unreported LSCC prognostic TFs - BCAT1, CHD4, FOXA2, GATA6, HNF1A, HOXB13, MAFF, and TCF4 - were screened via Kaplan-Meier curves. Cox analysis determined for the first time that HOXB13 expression and gender were independently associated with LSCC prognosis. Compared to control tissues, elevated expression of HOXB13 was found in LSCC tissues (standardized mean difference = 0.44, 95% confidence interval [0.13-0.76]). HOXB13 expression also makes it feasible to screen LSCC from non-LSCC (area under the curve = 0.77), and HOXB13 may play an essential role in LSCC by regulating HOXB7. In conclusion, HOXB13 may be a novel marker for LSCC clinical screening and treatment.


Assuntos
Biomarcadores Tumorais , Neoplasias de Cabeça e Pescoço , Carcinoma de Células Escamosas de Cabeça e Pescoço , Fatores de Transcrição , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Bases de Dados Genéticas , Feminino , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/mortalidade , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Humanos , Masculino , Prognóstico , Mapas de Interação de Proteínas/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
5.
Med Sci Monit ; 26: e928185, 2020 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-33361747

RESUMO

BACKGROUND Immune-related genes (IRGs) are closely related to the incidence and progression of tumors, potentially indicating that IRGs play an important role in laryngeal squamous cell carcinoma (LSCC). MATERIAL AND METHODS An RNA sequencing dataset containing 123 samples was collected from The Cancer Genome Atlas. Based on immune-related differentially expressed genes (IRDEGs), a potential molecular mechanism of LSCC was explored through analysis of information in the Gene Ontology (GO) resource and the Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein interactions (PPIs). A regulatory network of transcriptional regulators and IRDEGs was constructed to explore the underlying molecular mechanism of LSCC at the upstream level. Candidates from IRDEGs for signature were screened via univariate Cox analysis and using the least absolute shrinkage and selection operator (LASSO) technique. The IRDEG signature of LSCC was constructed by using a multivariate Cox proportional hazards model. RESULTS GO and KEGG analysis showed that IRDEGs may participate in the progression of LSCC through immune-related reactions. PPI analysis demonstrated that, among the IRDEGs in LSCC, the Kininogen 1; C-X-X motif chemokine ligand 10; elastase, neutrophil expressed; and LYZ genes are hub genes in the development of LSCC. At the upstream level, SPI1, SP140, signal transducer and activator of transcription 4, zinc finger E-box binding homeobox, and Ikaros family zinc finger 2 are the hub transcriptional regulators of IRDEGs. The risk score based on the IRDEG signature was able to distinguish prognosis in patients with LSCC and represents an independent prognostic risk factor for LSCC. CONCLUSIONS From the perspective of IRGs, we first constructed an IRDEG signature related to the prognosis of LSCC, which can be used as a novel marker to predict prognosis in patients with LSCC.


Assuntos
Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/imunologia , Regulação Neoplásica da Expressão Gênica , Neoplasias Laríngeas/genética , Neoplasias Laríngeas/imunologia , Carcinoma de Células Escamosas/diagnóstico , Perfilação da Expressão Gênica , Ontologia Genética , Redes Reguladoras de Genes , Humanos , Neoplasias Laríngeas/diagnóstico , Nomogramas , Prognóstico , Mapas de Interação de Proteínas/genética , Reprodutibilidade dos Testes , Fatores de Risco , Fatores de Transcrição/metabolismo , Regulação para Cima/genética
6.
Oncol Lett ; 20(6): 377, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33154775

RESUMO

Approximately 500,000 new head and neck squamous cell carcinoma (HNSCC) cases are detected every year around the world, and its incidence ranks sixth among all cancer types globally. Among these cases, oral squamous cell carcinoma (OSCC) and laryngeal squamous cell carcinoma (LSCC) are HNSCC subtypes with high incidence rates, especially in China. The present study examines the association between the apolipoprotein L1 (APOL1) mRNA and protein expression and clinical parameters in HNSCC. The two most common types (oral and larynx) of HNSCC were selected for subgroup analyses. Immunohistochemistry (IHC) was used to detect APOL1 protein expression levels in HNSCC clinical specimens. It was demonstrated that APOL1 protein expression in 221 cases of HNSCC was higher compared with that in normal tissues. Consistent upregulation of APOL1 protein was also found in subgroups of OSCC and LSCC. Through mining the ArrayExpress, The Cancer Genome Atlas and the Gene Expression Omnibus databases, microarrays and RNA sequencing data for HNSCC were retrieved, which were used to analyze APOL1 mRNA expression levels. The results showed that APOL1 expression was higher in both OSCC and LSCC subtypes, as well as in HNSCC, compared with that in non-cancerous squamous epithelium. The summary receiver operating characteristic analysis showed that APOL1 had potential as a diagnostic biomarker for HNSCC, OSCC and LSCC. Thus, upregulation of APOL1 may contribute to the tumorigenesis of HNSCC.

7.
Artigo em Inglês | MEDLINE | ID: mdl-33179959

RESUMO

Background: The expression level and clinical significance of integrin subunit beta 4 (ITGB4) in head and neck squamous cell carcinoma (HNSCC) remain unclear. Materials and Methods: Expression of ITGB4 in HNSCC tissues were evaluated by calculating standard mean differences (SMDs) based on gene chips, RNA-seq, and immunohistochemistry data (n = 2330) from multiple sources. Receiver operating characteristic (ROC) curves were used to detect the ability of ITGB4 to distinguish HNSCC from non-HNSCC samples. The relationship between the expression level of ITGB4 and clinical parameters was evaluated by calculating SMDs. Results: Identical results of mRNA and protein levels indicated remarkable up-expression of ITGB4 in HNSCC tissues. Further ROC curves showed that ITGB4 could distinguish HNSCC from non-HNSCC samples. Genetic alteration analysis of ITGB4 in HNSCC indicated that overexpression of ITGB4 in HNSCC was likely not owing to genetic alteration of ITGB4. Moreover, ITGB4 overexpression level may be correlated with clinical T stage. Conclusion: ITGB4 likely plays an essential role in HNSCC occurrence based on our study and its potential diagnostic value is worthy of further exploration in the future.

9.
Cancer Biomark ; 29(1): 111-124, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32623386

RESUMO

Interleukin 24 (IL24) has been documented to be highly expressed in several cancers, but its role in laryngeal squamous cell carcinoma (LSCC) remains unclarified. In this study, to reveal the function and its clinical significance of IL24 in LSCC, multiple detecting methods were used comprehensively. IL24 protein expression was remarkably higher in LSCC (n= 49) than non-cancerous laryngeal controls (n= 26) as detected by in-house immunohistochemistry. Meanwhile, the IL24 mRNA expression was also evaluated based on high throughput data from Gene Expression Omnibus, The Cancer Genome Atlas, ArrayExpress and Oncomine databases. Consistently with the protein level, IL24 mRNA expression level was also predominantly upregulated in LSCC (n= 172) compared to non-cancerous laryngeal tissues (n= 81) with the standard mean difference (SMD) being 1.25 and the area under the curve (AUC) of the summary receiver operating characteristic (sROC) being 0.89 (95% CI = 0.86-0.92). Furthermore, the related genes of IL24 and the differentially expressed genes (DEGs) of LSCC were intersected and sent for Gene ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and the protein-protein interaction (PPI) analyses. In the GO annotation, the top terms of biological process (BP), cellular component (CC) and molecular function (MF) were extracellular matrix organization, extracellular matrix, cytokine activity, respectively. The top pathway of KEGG was ECM-receptor interaction. The PPI networks indicated the top hub genes of IL24-related genes in LSCC were SERPINE1, TGFB1, MMP1, MMP3, CSF2, and ITGA5. In conclusion, upregulating expression of IL24 may enhance the occurrence of LSCC, which owns prospect diagnostic ability and therapeutic significance in LSCC.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/genética , Interleucinas/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/patologia , Biologia Computacional , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Redes Reguladoras de Genes/genética , Fator Estimulador de Colônias de Granulócitos e Macrófagos/genética , Humanos , Integrinas/genética , Masculino , Metaloproteinase 1 da Matriz/genética , Metaloproteinase 3 da Matriz/genética , MicroRNAs , Pessoa de Meia-Idade , Inibidor 1 de Ativador de Plasminogênio/genética , Mapas de Interação de Proteínas/genética , Transdução de Sinais/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Fator de Crescimento Transformador beta1/genética
10.
Med Sci Monit ; 26: e922854, 2020 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-32529991

RESUMO

BACKGROUND Oral squamous cell carcinoma (OSCC) is the sixth most prevalent cancer worldwide, with low 5-year survival rate. To identify novel prognostic markers for OSCC and determine the immune and stromal landscape of OSCC, a risk signature for OSCC patients was constructed in this study. MATERIAL AND METHODS Immune and stromal scores for OSCC samples from the Genomic Data Commons Data Portal were computed to delineate the tumor microenvironment landscape of oral cancer based on the Estimation of STromal and Immune cells in MAlignant Tumours using Expression data algorithm. An immune score-based risk signature was constructed by combining random forest and support vector machine methods. Correlation analysis of risk signature gene expression and immune cell infiltration was conducted, and the distinguishing power of individual signature genes was evaluated by analyzing receiver operating characteristics (ROC) curves. Differentially enriched pathways between high and low risk groups were investigated via gene set variation analysis. ROC curves were plotted for signature genes to examine their ability to distinguish the recurrence and survival status of OSCC patients from GSE84846. RESULTS An immune score-related risk signature composed of ARMH1, F2RL2, AC004687.1, COL6A5, AC008750.1, RAB19, CRLF2, GRIP2, and FAM162B performed well in the prognostic stratification of OSCC patients and could effectively distinguish their survival status. Lists of pathways, including cytokine-cytokine receptor interaction and cell adhesion molecules displayed remarkable differential enrichment between high and low risk OSCC patients. CONCLUSIONS An immune score-based risk signature constructed presently may be useful to decide appropriate treatment options for individual OSCC patients.


Assuntos
Neoplasias Bucais/genética , Neoplasias Bucais/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/imunologia , Citocinas/genética , Citocinas/imunologia , Bases de Dados Genéticas , Feminino , Perfilação da Expressão Gênica , Humanos , Sistema Imunitário/citologia , Sistema Imunitário/imunologia , Linfócitos do Interstício Tumoral , Masculino , Análise Multivariada , Prognóstico , Modelos de Riscos Proporcionais , Mapas de Interação de Proteínas , RNA Mensageiro , RNA-Seq , Curva ROC , Receptores de Citocinas/genética , Receptores de Citocinas/imunologia , Medição de Risco , Máquina de Vetores de Suporte , Transcriptoma , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia
11.
Biomed Res Int ; 2020: 2102785, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32280681

RESUMO

Background: To investigate the effects of robot-assisted gait training (RAGT) on spasticity and pain in people with spinal cord injury (SCI). Material and methods. Four electronic databases (PubMed, Scopus, Medline, and Cochrane Central Register of Controlled Trials) were searched for studies published up to November 2019. Only human trials and of English language were included. The searched studies were reviewed and extracted independently by two authors. Randomized controlled trials (RCTs) and non-RCTs were pooled separately for analyses. Primary outcome measures included spasticity assessed by Ashworth scale (AS) or modified Ashworth scale (MAS) and pain assessed by VAS. Secondary outcome measures included lower extremity motor score (LEMS) and walking ability (i.e., 6-minute walk test, 10-meter walk test). Results: A total of 225 studies were identified. Eighteen studies (7 RCTs and 11 non-RCTs) including 301 subjects met inclusion criteria. The outcome measure of spasticity significantly improved in favor of RAGT group in non-RCTs (AS: 95%CI = -0.202 to -0.068, p ≤ 0.001; MAS: 95%CI = -2.886 to -1.412, p ≤ 0.001). The results on pain did not show significant change after RAGT in either RCTs or non-RCTs. LEMS and walking ability significantly increased in favor of RAGT. Conclusions: RAGT can improve spasticity and walking ability in people with SCI. The probable reason for no significant change in pain after RAGT is floor effect. RAGT is beneficial for normalizing muscle tone and for improving lower extremity function in people with SCI without causing extra pain.


Assuntos
Marcha/fisiologia , Robótica , Traumatismos da Medula Espinal/reabilitação , Humanos , Extremidade Inferior/fisiologia , Espasticidade Muscular/reabilitação , Força Muscular , Ensaios Clínicos Controlados não Aleatórios como Assunto , Avaliação de Resultados em Cuidados de Saúde , Dor/reabilitação , Ensaios Clínicos Controlados Aleatórios como Assunto , Caminhada
12.
PeerJ ; 8: e8380, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32095320

RESUMO

Pancreatic adenocarcinoma (PAAD), the most common subtype of pancreatic cancer, is a highly lethal disease. In this study, we integrated the expression profiles of splicing factors (SFs) of PAAD from RNA-sequencing data to provide a comprehensive view of the clinical significance of SFs. A prognostic index (PI) based on SFs was developed using the least absolute shrinkage and selection operator (LASSO) COX analysis. The PI exhibited excellent performance in predicting the status of overall survival of PAAD patients. We also used the percent spliced in (PSI) value obtained from SpliceSeq software to quantify different types of alternative splicing (AS). The prognostic value of AS events was explored using univariate COX and LASSO COX analyses; AS-based PIs were also proposed. The integration of prognosis-associated SFs and AS events suggested the potential regulatory mechanisms of splicing processes in PAAD. This study defined the markedly clinical significance of SFs and provided novel insight into their potential regulatory mechanisms.

13.
Pathol Res Pract ; 216(2): 152785, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31889588

RESUMO

The relationship between integrin beta 4 (ITGB4) expression and laryngeal squamous cell carcinoma (LSCC) remains unclarified. The object of the present study was to explore the clinical significance and potential molecular mechanism of ITGB4 in LSCC. The protein level of ITGB4 was significantly higher in 46 LSCC patients than in 26 non-LSCC tissues detected by in-house immunohistochemistry. Consistently, ITGB4 mRNA level was also greatly upregulated based on microarray and RNA-seq data (standard mean difference, SMD = 1.62, 95 % CI: 1.23-2.00). And the area under curves (AUC) of summary receiver operator characteristic (SROC) was 0.87 (95 % CI: 0.84-0.90) based on 172 cases of LSCC and 59 cases of non-cancerous controls. Ninety genes were intersected by the ITGB4 related genes and LSCC differential expressed genes (DEGs) from all available microarray and RNA-seq datasets. Based on Gene Ontology (GO) analysis, the top terms of biological process (BP), cellular component (CC) and molecular function (MF) for the 90 ITGB4 related DEGs were extracellular matrix organization, basement membrane and extracellular matrix structural constituent, respectively. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that ITGB4 related DEGs mainly participated in the pathways of ECM-receptor interaction, Focal adhesion and Small cell lung cancer. Moreover, the Protein-Protein Interaction (PPI) network indicated that ITGA3, ITGA5, ITGB4, MET, LAMA3, and COL4A1 might be the core genes of LSCC development related to ITGB4. In conclusion, high ITGB4 expression may lead to the occurrence and development of LSCC via various signaling pathways.


Assuntos
Carcinoma de Células Escamosas/genética , Regulação Neoplásica da Expressão Gênica , Integrina beta4/metabolismo , Neoplasias Laríngeas/genética , Transdução de Sinais , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Feminino , Ontologia Genética , Humanos , Imuno-Histoquímica , Integrina beta4/genética , Neoplasias Laríngeas/metabolismo , Neoplasias Laríngeas/patologia , Laringe/patologia , Masculino , Análise em Microsséries , Pessoa de Meia-Idade , Mapeamento de Interação de Proteínas , Análise de Sequência de RNA
14.
Pathol Res Pract ; 216(1): 152754, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31787478

RESUMO

Breast cancer (BC) is the most common cancer worldwide. However, the expression and potential mechanism of miR-375 in BC are still controversial. We first collected microRNA chips and microRNA sequencing data from multiple databases for analyzing the expression level of miR-375, and further exploring the target genes and underlying molecular mechanism in BC. miR-375 in BC was predominantly overexpressed compared with that in normal breast tissues (pooled standard mean difference [SMD] = 0.49; 95 % confidence interval [CI]: 0.24-0.73, p < 0.0001). Meanwhile, the overall pooled area under the curve (AUC) in the summary receiver operating characteristic (SROC) of miR-375 was 0.83 (95 % CI = 0.79-0.86) based on 2928 cases of BC patients and 816 cases of controls, while the diagnostic positive likelihood ratio (DLR) positive and the DLR negative value were 3.90 (95 % CI = 2.46-6.19) and 0.39 (95 % CI = 0.28-0.54), respectively. The hazard ratios (HRs) were 1.29 (95 % CI = 1.04-1.6, P = 0.02) and 1.23 (95 % CI = 0.89-1.7, P = 0.22) for the cohorts of METABRIC and The Cancer Genome Atlas (TCGA). In vitro study demonstrated that miR-375 inhibitor could suppress the cell growth and induce apoptosis of BC cells. A total of 107 overlapping genes from microarrays after miR-375 transfection, the TCGA RNA sequencing, the microarrays of Affymetrix platform, and online predicting software were selected as the prospective targets of miR-375 in BC. Based on Gene Ontology (GO) enrichment analysis, the potential targets of miR-375 were notable for their somatic stem cell division, plasma membrane, and proline-rich region binding. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway examination demonstrated that the targets were associated with the pathways of prion diseases, proteoglycans in cancer, and focal adhesion. Then, 107 targets of miR-375 in BC were used to construct a protein-protein interaction (PPI) network. Finally, EGFR, PRKCA, PPARA, ADIPOQ, and ITSN1 were found to be the hub genes of miR-375. These targets showed negative correlations with miR-375 level. The upregulated miR-375 might play an essential part in the tumorigenesis and progression of BC.


Assuntos
Neoplasias da Mama/genética , Regulação Neoplásica da Expressão Gênica/genética , MicroRNAs/genética , Ativação Transcricional/genética , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/metabolismo , Simulação por Computador , Feminino , Perfilação da Expressão Gênica/métodos , Humanos , Mapas de Interação de Proteínas/genética , Curva ROC
15.
Int J Biol Sci ; 15(13): 2798-2814, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31853219

RESUMO

Disequilibrium of CD4+ T-cell subpopulations in peripheral blood (PB) of patients with primary immune thrombocytopenia (ITP) has been well established, whereas the profile of CD4+ T-cell subpopulations in bone marrow (BM) remains elusive. In the present study, the frequencies of T helper 22 (Th22), Th17, Th1, Th2, follicular T helper (Tfh) cells and regulatory T cells (Tregs) as well as their effector cytokines in BM and PB from active ITP patients and healthy controls (HCs) were determined. Results showed that the frequencies of Th22, Th17, Th1, and Tfh cells were significantly higher, but Treg number was remarkably lower in BM from ITP patients than from HCs. In the ITP group, it was notable that the numbers of BM Th22, Th17, Th1, Th2, and Tfh cells were significantly elevated compared with the matched PB counterparts, while Treg number in BM was considerably reduced compared with that in PB. In consistence with the BM Th subset pattern, plasma levels of interleukin (IL)-22, IL-17A, and interferon (INF)-γ in BM from ITP patients were significantly increased compared with that from HCs. Therefore, the balance of CD4+ T-cell subsets was disrupted in both BM and PB of ITP patients, suggesting that this might play important roles in the pathophysiological process of ITP.


Assuntos
Linfócitos T CD4-Positivos/metabolismo , Púrpura Trombocitopênica Idiopática/imunologia , Púrpura Trombocitopênica Idiopática/metabolismo , Linfócitos T Auxiliares-Indutores/metabolismo , Adulto , Idoso , Medula Óssea/metabolismo , Feminino , Citometria de Fluxo , Humanos , Masculino , Pessoa de Meia-Idade , Células Th1/metabolismo , Células Th17/metabolismo , Células Th2/metabolismo , Adulto Jovem
16.
Thromb Haemost ; 119(5): 758-765, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30808044

RESUMO

The binding of programmed death 1 (PD-1) to its ligands PD-L1 and PD-L2 on antigen-presenting cells turns off autoreactive T cells and induces peripheral tolerance. Aberrant PD-1/PD-L signalling could result in a breakdown of peripheral tolerance and lead to autoimmune diseases. In this study, we detected PD-1 and PD-L expression on T cells and dendritic cells (DCs) in immune thrombocytopenia (ITP) patients with active disease by flow cytometry. The effects of PD-L1-Fc fusion protein (PD-L1-Fc) on T cells and on secretion of interferon-γ (IFN-γ) and interleukin-2 (IL-2) were detected by flow cytometry and enzyme-linked immunosorbent assay, respectively. Compared with healthy controls, PD-1 expression was significantly increased in CD4+ T cells and CD8+ T cells from patients with active ITP. However, PD-L1 expression on monocyte-derived DCs was lower in patients with active ITP than in healthy controls. In vitro assays revealed that PD-L1-Fc increased T cell apoptosis, inhibited activation and proliferation of CD4+ T cells and CD8+ T cells and decreased IFN-γ and IL-2 secretion in patients with active ITP. These results suggest that the aberrant PD-1/PD-L negative co-stimulatory pathway may play a role in ITP. Enhancing PD-1/PD-L signalling might be a promising therapeutic approach for ITP patients by enhancing T cell apoptosis, inhibiting T cell activation and proliferation and reducing secretion of inflammatory factors.


Assuntos
Antígeno B7-H1/metabolismo , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Receptor de Morte Celular Programada 1/metabolismo , Púrpura Trombocitopênica Idiopática/metabolismo , Adolescente , Adulto , Idoso , Apoptose , Antígeno B7-H1/genética , Proliferação de Células , Células Cultivadas , Feminino , Humanos , Ativação Linfocitária/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/farmacologia , Transdução de Sinais , Regulação para Cima , Adulto Jovem
17.
Rapid Commun Mass Spectrom ; 32(16): 1462-1472, 2018 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-29740899

RESUMO

RATIONALE: Gas chromatography/mass spectrometry (GC/MS) is a routine and basic instrumental method for the analysis of complex coal conversion products in the chemical industry. To further enhance the practical potential of GC/MS in chemical industry, a tandem MS method for the selection of ion pairs applied in monitoring coal conversions was established using GC/quadrupole time-of-flight MS (GC/Q-TOF MS). The corresponding fragmentation pathways were explored and suitable ion pairs were screened. METHODS: Fourteen coal-related model compounds (CRMCs) were analyzed using GC/Q-TOF MS with different collision-induced dissociation (CID) energies (5-20 eV). The fragmentation pathways can offer a better understanding of chemical bond breaking, hydrogen transfer, rearrangement reactions and elimination of neutral fragments for CRMCs during the CID process. RESULTS: The precursor ions of aromatic hydrocarbons without alkyl chains were difficult to fragment with a CID energy of 20 eV. But aromatic hydrocarbons with branched chains were prone to fragment via the loss of alkyl chains and further fragmented through ring-opening reactions. Compared with the Calk Car bond, the Car Car bond was difficult to fragment due to its high bond dissociation energy. The existence of heteroatoms facilitated fragmentation that was conducive to the screening of ion pairs. CONCLUSIONS: The CID technique of GC/Q-TOF MS will contribute to studies on the organic composition of coals and to building monitoring methods for coal conversions via fragmentation and ion pair selection.

18.
Cytokine ; 92: 110-117, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28142109

RESUMO

Thrombopoietin receptor agonists (TPO-RAs) have been clinically used in primary immune thrombocytopenia (ITP) with favorable outcomes, while their effect on cytokine regulation in ITP remains unknown. In the present study, plasma and mRNA expression levels of interleukin (IL)-2, interferon gamma (IFN-γ), IL-4, IL-17A, and transforming growth factor-ß1 (TGF-ß1) were determined by ELISA and real-time quantitative PCR in 26 corticosteroid-resistant/relapsed ITP patients receiving eltrombopag or rhTPO therapy and 15 healthy controls (HCs). Results showed that plasma and mRNA levels of IL-2, IFN-γ, IL-4, and IL-17A in ITP patients did not change significantly after TPO-RA treatment, whereas TGF-ß1 levels increased remarkably. The pre- and post-treatment plasma and mRNA levels of IFN-γ and IL-2 were significantly higher, while the pre- and post-treatment IL-4 levels as well as the pre-treatment TGF-ß1 levels were remarkably lower in ITP patients compared with HCs. There was no significant difference in TGF-ß1 levels between TPO-RA-treated ITP patients and HCs. No statistical difference was found in plasma levels of IL-17A between ITP patients before or after treatment and HCs. However, the pre- and post-treatment mRNA expression of IL-17A and retinoic orphan receptor (ROR) γt in ITP patients were higher than that in HCs. Overall, these findings indicated that TPO-RA treatment could promote the secretion of TGF-ß1, while it could not correct the Th1 and Th17 polarization in ITP patients. This study might improve our understanding of the mechanism of action of TPO-RAs and provide important information for optimizing therapeutic strategies for ITP.


Assuntos
Benzoatos/administração & dosagem , Citocinas/sangue , Hidrazinas/administração & dosagem , Púrpura Trombocitopênica Idiopática/sangue , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Pirazóis/administração & dosagem , Receptores de Trombopoetina/agonistas , Trombopoetina/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/sangue , Células Th1/metabolismo , Células Th17/metabolismo
19.
Oncotarget ; 8(4): 6142-6154, 2017 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-28008152

RESUMO

Acquired aplastic anemia is an idiopathic paradigm of human bone marrow failure syndrome, which involves active destruction of hematopoietic stem cells and progenitors by cytotoxic T cells in the bone marrow. Aberrant expression of microRNAs in T cells has been shown to lead to development of certain autoimmune diseases. In the present study, we performed a microarray analysis of miRNA expression in bone marrow CD3+ T cells from patients with aplastic anemia and healthy controls. Overexpression of miR34a and underexpression of its target gene diacylglycerol kinase (DGK) ζ in bone marrow mononuclear cells were validated in 41 patients and associated with the severity of aplastic anemia. Further, the level of miR34a was higher in naïve T cells from patients than from controls. The role of miR34a and DGKζ in aplastic anemia was investigated in a murine model of immune-mediated bone marrow failure using miR34a-/- mice. After T-cell receptor stimulation in vitro, lymph node T cells from miR34a-/- mice demonstrated reduced activation and proliferation accompanied with a less profound down-regulation of DGKζ expression and decreased ERK phosphorylation compared to those from wild-type C57BL6 control mice. Infusion of 5 × 106 miR34a-/- lymph node T cells into sublethally irradiated CB6F1 recipients led to increased Lin-Sca1+CD117+ cells and less vigorous expansion of CD8+ T cells than injection of same number of wild-type lymph node cells. Our study demonstrates that the miR34a/DGKζ dysregulation enhances T-cell activation in aplastic anemia and targeting miR34a may represent a novel molecular therapeutic approach for patients with aplastic anemia.


Assuntos
Anemia Aplástica/genética , Diacilglicerol Quinase/genética , MicroRNAs/genética , Linfócitos T/imunologia , Anemia Aplástica/imunologia , Animais , Complexo CD3/metabolismo , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Ativação Linfocitária , Masculino , Camundongos , Transplante de Neoplasias , Análise de Sequência com Séries de Oligonucleotídeos
20.
Int J Anal Chem ; 2017: 9298523, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29387086

RESUMO

Elucidation of chemical composition of biooil is essentially important to evaluate the process of lignocellulosic biomass (LCBM) conversion and its upgrading and suggest proper value-added utilization like producing fuel and feedstock for fine chemicals. Although the main components of LCBM are cellulose, hemicelluloses, and lignin, the chemicals derived from LCBM differ significantly due to the various feedstock and methods used for the decomposition. Biooil, produced from pyrolysis of LCBM, contains hundreds of organic chemicals with various classes. This review covers the methodologies used for the componential analysis of biooil, including pretreatments and instrumental analysis techniques. The use of chromatographic and spectrometric methods was highlighted, covering the conventional techniques such as gas chromatography, high performance liquid chromatography, Fourier transform infrared spectroscopy, nuclear magnetic resonance, and mass spectrometry. The combination of preseparation methods and instrumental technologies is a robust pathway for the detailed componential characterization of biooil. The organic species in biooils can be classified into alkanes, alkenes, alkynes, benzene-ring containing hydrocarbons, ethers, alcohols, phenols, aldehydes, ketones, esters, carboxylic acids, and other heteroatomic organic compounds. The recent development of high resolution mass spectrometry and multidimensional hyphenated chromatographic and spectrometric techniques has considerably elucidated the composition of biooils.

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