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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.
Artigo em Inglês | MEDLINE | ID: mdl-34619053

RESUMO

Background: To date, the clinical management of advanced hepatocellular carcinoma (HCC) patients remains tough and the mechanisms of E2F transcription factor 1 (E2F1) underlying HCC are obscure. Materials and Methods: Our study integrated datasets mined from several public databases to comprehensively understand the deregulated expression status of E2F1. Tissue microarrays and immunohistochemistry staining was used to validate E2F1 expression level. The prognostic value of E2F1 was assessed. In-depth subgroup analyses were implemented to compare the differentially expressed levels of E2F1 in HCC patients with various tumor stages. Functional enrichments were used to address the predominant targets of E2F1 and shedding light on their potential roles in HCC. Results: We confirmed the elevated expression of E2F1 in HCC. Subgroup analyses indicated that elevated E2F1 level was independent of various stages in HCC. E2F1 possessed moderate discriminatory capability in differentiating HCC patients from non-HCC controls. Elevated E2F1 correlated with Asian race, tumor classification, neoplasm histologic grade, eastern cancer oncology group, and plasma AFP levels. Furthermore, high E2F1 correlated with poor survival condition and pooled HR signified E2F1 as a risk factor for HCC. Enrichment analysis of differentially expressed genes, coexpressed genes, and putative targets of E2F1 emphasized the importance of cell cycle pathway, where CCNE1 and CCNA2 served as hub genes. Conclusions: We confirmed the upregulation of E2F1 and explored the prognostic value of E2F1 in HCC patients. Two putative targeted genes (CCNE1 and CCNA2) of E2F1 were identified for their potential roles in regulating cell cycle and promote antiapoptotic activity in HCC patients.

3.
IET Syst Biol ; 15(1): 1-13, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33527765

RESUMO

The clinicopathological implication and prospective molecular mechanisms of miRNA-145-5p in the metastasis of prostate cancer (PCa) stand unclear. Herein, it is found that miRNA-145-5p expression was remarkably reduced in 131 cases of metastatic PCa than 1371 cases of localised ones, as the standardised mean differences (SMD) was -1.26 and the area under the curve (AUC) was 0.86, based on miRNA-chip and miRNA-sequencing datasets. The potential targets of miRNA-145-5p in metastatic PCa (n = 414) was achieved from the intersection of miRNA-145-5p transfected metastatic PCa cell line data, differential expression of metastatic PCa upregulated genes and online prediction databases. TOP2A was screened as one of the target hub genes by PPI network analysis, which was adversely related to miRNA-145-5p expression in both metastatic PCa (r = -0.504) and primary PCa (r = -0.281). Gene-chip and RNA-sequencing datasets, as well as IHC performed on clinical PCa samples, showed consistent upregulated expression of TOP2A mRNA and protein in PCa compared with non-PCa. The expression of TOP2A mRNA was also significantly higher in metastatic than localised PCa with the SMD being 1.72 and the AUC of sROC being 0.91. In summary, miRNA-145-5p may participate in PCa metastasis by binding TOP2A and be useful as a biomarker for the detection of metastatic PCa.

4.
Med Sci Monit ; 27: e928800, 2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33622998

RESUMO

BACKGROUND Hepatocellular carcinoma (HCC) causes a heavy disease burden worldwide. Cell division cycle 45 (Cdc45) and its encoding gene (CDC45) have been studied for a long time, but their expression patterns and roles in liver carcinogenesis and advanced HCC deterioration are still incompletely understood. This study integrated tissue microarray and bioinformatics analyses to explore the expression and clinical value of CDC45 and Cdc45 in HCC. MATERIAL AND METHODS In HCC, the expression and relationships with clinic-pathological parameters of CDC45 and Cdc45 were investigated by integrating the RNA-sequencing data, downloaded from The Cancer Genome Atlas and Oncomine databases, and tissue microarray with immunohistochemistry staining. Co-expressed genes and genetic alterations of CDC45 separately obtained from Oncomine and cBioPortal databases were identified to shed light on the potential mechanisms of CDC45 in HCC. RESULTS CDC45 and Cdc45 were both overexpressed in HCC tissues, and the CDC45 level progressively increased from stage I to III. The survival outcomes of the group with high CDC45 expression were significantly worse compared with the group with low expression. Amplification and deep deletion were 2 major significant alteration types in HCC patients, and the outcomes were worse in patients with altered versus unaltered CDC45. NUDT1, E2F1, CCNE2, MCM5, and CENPM were identified as the most significantly co-expressed genes. CONCLUSIONS CDC45 and Cdc45 were both upregulated in HCC, and increased expression levels and genetic alternations of CDC45 were correlated with worse prognosis in HCC patients. CDC45 may promote HCC by co-expressing with NUDT1, E2F1, CCNE2, MCM5, and CENPM.


Assuntos
Carcinoma Hepatocelular/genética , Proteínas de Ciclo Celular/genética , Biomarcadores Tumorais/genética , Proteínas de Ciclo Celular/metabolismo , Biologia Computacional/métodos , Expressão Gênica , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/genética , Prognóstico , Análise de Sequência de RNA , Transcriptoma
5.
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.

6.
IET Syst Biol ; 14(5): 252-260, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33095746

RESUMO

This study aimed to investigate the clinicopathological significance and prospective molecular mechanism of RUNX family transcription factor 2 (RUNX2) in lung squamous cell carcinoma (LUSC). The authors used immunohistochemistry (IHC), RNA-seq, and microarray data from multi-platforms to conduct a comprehensive analysis of the clinicopathological significance and molecular mechanism of RUNX2 in the occurrence and development of LUSC. RUNX2 expression was significantly higher in 16 LUSC tissues than in paired non-cancerous tissues detected by IHC (P < 0.05). RNA-seq data from the combination of TCGA and genotype-tissue expression (GTEx) revealed significantly higher expression of RUNX2 in 502 LUSC samples than in 476 non-cancer samples. The expression of RUNX2 protein was also significantly higher in pathologic T3-T4 than in T1-T2 samples (P = 0.031). The pooled standardised mean difference (SMD) for RUNX2 was 0.87 (95% CI, 0.58-1.16), including 29 microarrays from GEO and one from ArrayExpress. The co-expression network of RUNX2 revealed complicated connections between RUNX2 and 45 co-expressed genes, which were significantly clustered in pathways including ECM-receptor interaction, focal adhesion, protein digestion and absorption, human papillomavirus infection and PI3K-Akt signalling pathway. Overexpression of RUNX2 plays an essential role in the clinical progression of LUSC.


Assuntos
Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Humanos , Análise de Sequência com Séries de Oligonucleotídeos
7.
Cancer Med ; 9(21): 8004-8019, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32931665

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) remains one of the most common cancers worldwide and tends to be detected at an advanced stage. More effective biomarkers for HCC screening and prognosis assessment are needed and the mechanisms of HCC require further exploration. The role of MAOA in HCC has not been intensively investigated. METHODS: In-house tissue microarrays, genechips, and RNAsequencing datasets were integrated to explore the expression status and the clinical value of MAOA in HCC. Immunohistochemical staining was utilized to determine MAOA protein expression. Intersection genes of MAOA related co-expressed genes and differentially expressed genes were obtained to perform functional enrichment analyses. In vivo experiment was conducted to study the impact of traditional Chinese medicine nitidine chloride (NC) on MAOA in HCC. RESULTS: MAOA was downregulated and possessed an excellent discriminatory capability in HCC patients. Decreased MAOA correlated with poor prognosis in HCC patients. Downregulated MAOA protein was relevant to an advanced TNM stage in HCC patients. Co-expressed genes that positively related to MAOA were clustered in chemical carcinogenesis, where CYP2E1 was identified as the hub gene. In vivo experiment showed that nitidine chloride significantly upregulated MAOA in a nude mouse HCC model. CONCLUSIONS: A decreased MAOA level is not only correlated with aggressive behaviors in males but also serves as a promising biomarker for the diagnosis and prognosis of HCC patients. Moreover, MAOA may play a role in AFB1 toxic transformation through its synergistic action with co-expressed genes, especially CYP3A4. MAOA also serves as a potential therapy target of NC in HCC patients.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma Hepatocelular/enzimologia , Neoplasias Hepáticas/enzimologia , Monoaminoxidase/análise , Animais , Antineoplásicos Fitogênicos/farmacologia , Benzofenantridinas/farmacologia , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Citocromo P-450 CYP2E1/genética , Citocromo P-450 CYP2E1/metabolismo , Citocromo P-450 CYP3A/genética , Citocromo P-450 CYP3A/metabolismo , Bases de Dados Genéticas , Regulação para Baixo , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Imuno-Histoquímica , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Camundongos Nus , Monoaminoxidase/genética , Estadiamento de Neoplasias , Análise de Sequência com Séries de Oligonucleotídeos , Valor Preditivo dos Testes , Mapas de Interação de Proteínas , RNA-Seq , Análise Serial de Tecidos , Ensaios Antitumorais Modelo de Xenoenxerto
8.
Ann Surg Treat Res ; 99(2): 118-126, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32802817

RESUMO

Purpose: This study was performed to establish and validate a nomogram for predicting the overall survival in children with neuroblastoma. Methods: The latest clinical data of neuroblastoma in Surveillance, Epidemiology, and End Results (SEER) database was extracted from 2000 to 2016. The cases included were randomly divided into training and validation cohorts. The survival curves were drawn with a Kaplan-Meier estimator to investigate the influences of certain single factors on overall survival. Also, least absolute shrinkage and selection operator regression was applied to further select the prognostic variables for neuroblastoma. Additionally, receiver operating characteristic (ROC) curves and calibration curves were used to evaluate the accuracy of the nomogram. Results: In total, 1,262 patients were collected and 8 independent prognostic factors were achieved, including patients' age, sex, race, tumor grade, radiotherapy, chemotherapy, tumor site, and tumor size. Then we constructed a nomogram by using the data of the training cohort with 886 cases. Subsequently, the nomogram was validated internally and externally with 886 and 376 cases, respectively. The internal validation revealed that the area under the curves (AUC) of ROC curves of 1-, 3-, and 5-year overall survival were 0.69, 0.78, and 0.81, respectively. Accordingly, the external validation also showed that the AUC of 1-, 3-, and 5-year overall survival were all ≥0.69. Both methods of validation demonstrated that the predictive calibration curves were consistent with standard curves. Conclusion: The nomogram possess the potential to be a new tool in predicting the survival rate of neuroblastoma patients.

9.
FEBS Open Bio ; 10(8): 1624-1641, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32598517

RESUMO

Lung squamous cell carcinoma (LUSC) is the main pathological type of pulmonary malignant tumors; at present, less than 10% of patients with advanced metastatic LUSC live for more than 5 years. We previously reported that low expression of miRNA-126-3p is associated with the occurrence and progression of lung adenocarcinoma (LUAD). Here, we examined expression of miRNA-126-3p in 23 samples from patients with LUSCs and 23 normal control specimens by quantitative real-time PCR (RT-qPCR). Associations between miRNA-126-3p expression and clinical features were studied from materials derived from Gene Expression Omnibus (GEO) chips and The Cancer Genome Atlas (TCGA) database. Twelve online platforms were used to identify candidate target genes of miRNA-126-3p. Further analyses of the Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and protein-protein interaction (PPI) network were performed on the target genes. GEO microarray analysis, TCGA data mining, RT-qPCR, and integration analysis consistently reported low expression of miRNA-126-3p in LUSC. A total of 42 genes were identified as potential target genes of miRNA-126-3p from online platforms, GEO microarrays, and the TCGA database. GO and KEGG analyses demonstrated that the target genes are involved in several biological processes that promote the progression of LUSC. SOX2, E2F2, and E2F3 were selected as hub genes from the PPI network for further analysis. In summary, our results suggest that the low expression of miRNA-126-3p may play a role in promoting the development of LUSC and miRNA-126-3p may be a biomarker for LUSC early diagnosis and prognosis.

10.
Nucleic Acids Res ; 48(10): e57, 2020 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-32232370

RESUMO

Site-specific DNA double-strand breaks have been used to generate knock-in through the homology-dependent or -independent pathway. However, low efficiency and accompanying negative impacts such as undesirable indels or tumorigenic potential remain problematic. In this study, we present an enhanced reduced-risk genome editing strategy we named as NEO, which used either site-specific trans or cis double-nicking facilitated by four bacterial recombination factors (RecOFAR). In comparison to currently available approaches, NEO achieved higher knock-in (KI) germline transmission frequency (improving from zero to up to 10% efficiency with an average of 5-fold improvement for 8 loci) and 'cleaner' knock-in of long DNA fragments (up to 5.5 kb) into a variety of genome regions in zebrafish, mice and rats. Furthermore, NEO yielded up to 50% knock-in in monkey embryos and 20% relative integration efficiency in non-dividing primary human peripheral blood lymphocytes (hPBLCs). Remarkably, both on-target and off-target indels were effectively suppressed by NEO. NEO may also be used to introduce low-risk unrestricted point mutations effectively and precisely. Therefore, by balancing efficiency with safety and quality, the NEO method reported here shows substantial potential and improves the in vivo gene-editing strategies that have recently been developed.


Assuntos
Proteínas de Bactérias/metabolismo , Edição de Genes/métodos , Animais , Quebras de DNA de Cadeia Dupla , Proteínas de Ligação a DNA/metabolismo , Feminino , Técnicas de Introdução de Genes , Genômica , Recombinação Homóloga , Humanos , Mutação INDEL , Macaca fascicularis , Camundongos , Ratos Sprague-Dawley , Recombinases Rec A/metabolismo , Peixe-Zebra/genética
11.
Med Sci Monit ; 26: e920725, 2020 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-32214060

RESUMO

BACKGROUND Wilms tumor, or nephroblastoma, is a malignant pediatric embryonal renal tumor that has a poor prognosis. This study aimed to use bioinformatics data, RNA-sequencing, connectivity mapping, molecular docking, and ligand-protein binding to identify potential targets for drug therapy in Wilms tumor. MATERIAL AND METHODS Wilms tumor and non-tumor samples were obtained from high throughput gene expression databases, and differentially expressed genes (DEGs) were analyzed using the voom method in the limma package. The overlapping DEGs were obtained from the intersecting drug target genes using the Connectivity Map (CMap) database, and systemsDock was used for molecular docking. Gene databases were searched for gene expression profiles for complementary analysis, analysis of clinical significance, and prognosis analysis to refine the study. RESULTS From 177 cases of Wilms tumor, there were 648 upregulated genes and 342 down-regulated genes. Gene Ontology (GO) enrichment analysis showed that the identified DEGs that affected the cell cycle. After obtaining 21 candidate drugs, there were seven overlapping genes with 75 drug target genes and DEGs. Molecular docking results showed that relatively high scores were obtained when retinoic acid and the cyclin-dependent kinase inhibitor, alsterpaullone, were docked to the overlapping genes. There were significant standardized mean differences for three overlapping genes, CDK2, MAP4K4, and CRABP2. However, four upregulated overlapping genes, CDK2, MAP4K4, CRABP2, and SIRT1 had no prognostic significance. CONCLUSIONS RNA-sequencing, connectivity mapping, and molecular docking to investigate ligand-protein binding identified retinoic acid and alsterpaullone as potential drug candidates for the treatment of Wilms tumor.


Assuntos
Antineoplásicos/uso terapêutico , Avaliação Pré-Clínica de Medicamentos , Simulação de Acoplamento Molecular , Análise de Sequência de RNA , Tumor de Wilms/tratamento farmacológico , Antineoplásicos/farmacologia , Regulação Neoplásica da Expressão Gênica , Ontologia Genética , Humanos , Estimativa de Kaplan-Meier , Ligantes , Prognóstico , Ligação Proteica , Curva ROC , Tumor de Wilms/genética
12.
PeerJ ; 8: e8409, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32095323

RESUMO

Background: Hepatocellular carcinoma (HCC) is the second-highest cause of malignancy-related death worldwide, and many physiological and pathological processes, including cancer, are regulated by microRNAs (miRNAs). miR-193a-3p is an anti-oncogene that plays an important part in health and disease biology by interacting with specific targets and signals. Methods: In vitro assays were performed to explore the influences of miR-193a-3p on the propagation and apoptosis of HCC cells. The sequencing data for HCC were obtained from The Cancer Genome Atlas (TCGA), and the expression levels of miR-193a-3p in HCC and non-HCC tissues were calculated. The differential expression of miR-193a-3p in HCC was presented as standardized mean difference (SMD) with 95% confidence intervals (CIs) in Stata SE. The impact of miR-193a-3p on the prognoses of HCC patients was determined by survival analysis. The potential targets of miR-193a-3p were then predicted using miRWalk 2.0 and subjected to enrichment analyses, including Gene Ontology (GO) annotation, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and Protein-Protein Interaction (PPI) network analysis. The interaction between miR-193a-3p and one predicted target, Cyclin D1 (CCND1), was verified by dual luciferase reporter assays and Pearson correlation analysis. Results: MiR-193a-3p inhibited the propagation and facilitated the apoptosis of HCC cells in vitro. The pooled SMD indicated that miR-193a-3p had a low level of expression in HCC (SMD: -0.88, 95% CI [-2.36 -0.59]). Also, HCC patients with a higher level of miR-193a-3p expression tended to have a favorable overall survival (OS: HR = 0.7, 95% CI [0.43-1.13], P = 0.14). For the KEGG pathway analysis, the most related pathway was "proteoglycans in cancer", while the most enriched GO term was "protein binding". The dual luciferase reporter assays demonstrated the direct interaction between miR-193a-3p and CCND1, and the Pearson correlation analysis suggested that miR-193a-3p was negatively correlated with CCND1 in HCC tissues (R =  - 0.154, P = 0.002). Conclusion: miR-193a-3p could suppress proliferation and promote apoptosis by targeting CCND1 in HCC cells. Further, miR-193a-3p can be used as a promising biomarker for the diagnosis and treatment of HCC in the future.

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.
Front Neurosci ; 13: 639, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31281237

RESUMO

Purpose: This study examined the utilization of multiple types of acoustic information in lexical tone production and perception by pediatric cochlear implant (CI) recipients who are native speakers of Mandarin Chinese. Methods: Lexical tones were recorded from CI recipients and their peers with normal hearing (NH). Each participant was asked to produce a disyllabic word, yan jing, with which the first syllable was pronounced as Tone 3 (a low dipping tone) while the second syllable was pronounced as Tone 1 (a high level tone, meaning "eyes") or as Tone 4 (a high falling tone, meaning "eyeglasses"). In addition, a parametric manipulation in fundamental frequency (F0) and duration of Tones 1 and 4 used in a lexical tone recognition task in Peng et al. (2017) was adopted to evaluate the perceptual reliance on each dimension. Results: Mixed-effect analyses of duration, intensity, and F0 cues revealed that NH children focused exclusively on marking distinct F0 contours, while CI participants shortened Tone 4 or prolonged Tone 1 to enhance their contrast. In line with these production strategies, NH children relied primarily on F0 cues to identify the two tones, whereas CI children showed greater reliance on duration cues. Moreover, CI participants who placed greater perceptual weight on duration cues also tended to exhibit smaller changes in their F0 production. Conclusion: Pediatric CI recipients appear to contrast the secondary acoustic dimension (duration) in addition to F0 contours for both lexical tone production and perception. These findings suggest that perception and production strategies of lexical tones are well coupled in this pediatric CI population.

15.
Oncol Rep ; 42(1): 151-175, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31059074

RESUMO

Breast cancer (BC) has a complex etiology and pathogenesis, and is the most common malignant tumor type in females, in USA in 2018, yet its relevant molecular mechanisms remain largely unknown. The collagen type V α­1 chain (COL5A1) gene is differentially expressed in renal and ovarian cancer. Using bioinformatics methods, COL5A1 was determined to also be a significant gene in BC, but its association with BC has not been sufficiently reported. COL5A1 microarray and relevant clinical data were collected from the Gene Expression Omnibus, The Cancer Genome Atlas and other databases to summarize COL5A1 expression in BC and its subtypes at the mRNA and protein levels. All associated information was comprehensively analyzed by various software. The clinical significance of the mutation was obtained via the cBioPortal. Furthermore, Gene Ontology functional annotation and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were also performed to investigate the mechanism of COL5A1 in BC. Immunohistochemistry was also conducted to detect and confirm COL5A1 expression. It was determined that COL5A1 was highly expressed in BC tissues, compared with normal tissues at the mRNA level [standard mean difference, 0.84; 95% confidence interval (CI), 0.60­1.07; P=0.108]. The area under the summary receiver operator characteristic curve for COL5A1 was 0.87 (95% CI, 0.84­0.90). COL5A1 expression was altered in 32/817 (4%) sequenced samples. KEGG analysis confirmed the most notable pathways, including focal adhesion, extracellular matrix­receptor interaction and regulation of the actin cytoskeleton. Immunohistochemical detection was used to verify the expression of COL5A1 in 136 selected cases of invasive BC tissues and 55 cases of adjacent normal tissues, while the rate of high expression of COL5A1 in BC was up to 90.4%. These results indicated that COL5A1 is highly expressed at the mRNA and protein levels in BC, and the prognosis of patients with BC with high COL5A1 expression may be reduced; therefore, COL5A1 may be used independently or combined with other detection factors in BC diagnosis.


Assuntos
Neoplasias da Mama/metabolismo , Colágeno Tipo V/genética , Colágeno Tipo V/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Análise de Sequência de RNA/métodos , Adulto , Idoso , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Mapas de Interação de Proteínas , Curva ROC , Análise de Sobrevida , Regulação para Cima
16.
Pathol Res Pract ; 215(7): 152424, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31103408

RESUMO

BACKGROUND AND AIM: Extensive research has revealed that microRNAs (miRNAs) play a principle role in cancer, and miRNAs associated with specific cancers have also been identified. The role of microRNA (miR)-302b-5p, which is one of the miRNAs reported in association with cancer, in hepatocellular carcinoma (HCC) is still unclear. Thus, the present study aimed to reveal the expression and potential molecule mechanism of miR-302b-5p in HCC. METHODS: An extensive meta-analysis of data from real-time reverse transcription quantitative polymerase chain reaction (RT-qPCR), Gene Expression Omnibus and ArrayExpress microarrays was used to determine the expression of miR-302b-5p in HCC tissue samples and non-cancerous liver tissue samples. The sensitivity and specificity of miR-302b-5p as an indicator of HCC was estimated by plotting the receiver operating characteristic (ROC) and summarized ROC (sROC). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were employed to unravel the molecular mechanisms and biological functions of miR-302b-5p in HCC. Further, the putative target genes of miR-302b-5p were harvested based on the predicted genes and differentially expressed genes in HCC. Finally, the protein-protein interaction (PPI) network was built to determine the hub genes. RESULTS: According to the RT-qPCR results, the expression of miR-302b-5p was pronouncedly decreased in 39 HCC tissue samples as compared to 39 non-cancerous liver tissue samples. The standard mean difference (SMD) values of all the samples used in the meta-analysis also indicated lower miR-302b-5p expression in the 558 HCC tissue samples than in the 286 non-cancerous liver tissue samples. ROC and sROC analyses showed that miR-302b-5p had good specificity and sensitivity for distinguishing HCC tissue from non-cancerous liver tissue. Bioinformatics analyses identified 227 putative genes, and these genes were evidently enriched in the processes of organelle fission, chromosome and chromatin binding and were centralized in a "lysosome" pathway. The PPI network indicated that DNA topoisomerase II alpha (TOP2 A) was the most prominent hub gene of miR-302b-5p in HCC. Interestingly, according to the TCGA and Genotype-Tissue Expression databases, the mRNA and protein expression of TOP2 A were both elevated in HCC tissue samples as compared to non-cancerous liver tissue samples, and the overall survival and disease-free survival revealed that a high level of TOP2 A might reflect poor HCC outcome. CONCLUSIONS: Our findings indicate that miR-302b-5p might suppress HCC progression, and TOP2 A might be a potential target of miR-302b-5p in HCC. However, in-depth in vivo and in vitro experiments are required to verify these findings and explore the mechanisms involved.


Assuntos
Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Fígado/metabolismo , MicroRNAs/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Simulação por Computador , DNA Topoisomerases Tipo II/genética , DNA Topoisomerases Tipo II/metabolismo , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Humanos , Fígado/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , MicroRNAs/genética
17.
Sci Rep ; 9(1): 109, 2019 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-30643156

RESUMO

In tonal languages, voice pitch inflections change the meaning of words, such that the brain processes pitch not merely as an acoustic characterization of sound but as semantic information. In normally-hearing (NH) adults, this linguistic pressure on pitch appears to sharpen its neural encoding and can lead to perceptual benefits, depending on the task relevance, potentially generalizing outside of the speech domain. In children, however, linguistic systems are still malleable, meaning that their encoding of voice pitch information might not receive as much neural specialization but might generalize more easily to ecologically irrelevant pitch contours. This would seem particularly true for early-deafened children wearing a cochlear implant (CI), who must exhibit great adaptability to unfamiliar sounds as their sense of pitch is severely degraded. Here, we provide the first demonstration of a tonal language benefit in dynamic pitch sensitivity among NH children (using both a sweep discrimination and labelling task) which extends partially to children with CI (i.e., in the labelling task only). Strong age effects suggest that sensitivity to pitch contours reaches adult-like levels early in tonal language speakers (possibly before 6 years of age) but continues to develop in non-tonal language speakers well into the teenage years. Overall, we conclude that language-dependent neuroplasticity can enhance behavioral sensitivity to dynamic pitch, even in extreme cases of auditory degradation, but it is most easily observable early in life.


Assuntos
Implantes Cocleares , Audição , Idioma , Discriminação da Altura Tonal , Percepção da Altura Sonora , Adolescente , Comportamento , Criança , Humanos , Plasticidade Neuronal , Adulto Jovem
18.
Int J Clin Exp Pathol ; 12(11): 4041-4056, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31933800

RESUMO

BACKGROUND: The implication of miR-452-5p and its prospective machinery in hepatocellular carcinoma (HCC) remains largely unknown. For this reason, this study aimed to inspect the clinical implication of miR-452-5p expression in HCC tissues with multiple detection approaches, to analyze its potential function via in silico methods, and to validate this using a dual-luciferase reporter assay. METHODS: The assessment of the expression level of miR-452-5p in HCC was conducted via four methods: 1) in-house real-time quantitative PCR (RT-qPCR), 2) miRNA-sequencing (miRNA-seq) from The Cancer Genome Atlas (TCGA), 3) miRNA microarrays from the Gene Expression Omnibus (GEO), and 4) comprehensive meta-analyses calculating the standard mean difference (SMD) and summary of receiver operator characteristic (sROC). Following the target prediction, one of the potential targets of miR-452-5p was validated through a dual-luciferase reporter assay. RESULTS: MiR-452-5p was consistently elevated in HCC tissues via various detection methods, including in-house RT-qPCR, miRNA-seq, and miRNA microarrays. The final SMD was 0.842 for 820 cases of HCC samples. Simultaneously, the area under curve (AUC) of the sROC was 0.80 (0.76-0.83). The 1,135 predicted targets of miR-452-5p were enriched in the pathways of cytokine-cytokine receptor interaction, carbon metabolism, and complement and coagulation cascades. Among these predicted targets, CDKN1B was verified to be a real target of miR-452-5p. CONCLUSION: The overexpression of miR-452-5p may play a pivotal role in the carcinogenesis of HCC via targeting multiple signaling pathways and genes. The function and molecular machinery of miR-452-5p in HCC requires further in-depth exploration.

19.
Int J Clin Exp Pathol ; 12(4): 1439-1456, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31933962

RESUMO

BACKGROUND: The miR-191-5p expression has been reported to increase in hepatocellular carcinoma (HCC), but its clinical value and exact role remain to be further clarified. Thus, a comprehensive analysis was performed in the current study to explore the underlying function of miR-191-5p in HCC. METHODS: HCC-related expression data were collected to conduct a thorough analysis to determine the miR-191-5p expression and its clinical significance in HCC, including microarray data from the Gene Expression Omnibus and ArrayExpress database as well as quantitative real-time polymerase chain reaction (qRT-PCR) data of 178 matched clinical samples. The underlying relationship between miR-191-5p and HCC was also explored on the basis of a series of bioinformatics analyses. RESULTS: The overall pooled meta-analysis showed an overexpression of miR-191-5p in the HCC samples (SMD=0.400, 95% CI=0.139-0.663, P=0.003), consistent with the detected result of the clinical HCC samples through the qRT-PCR analysis. Higher miR-191-5p levels were correlated with advanced TNM stages (III and IV), higher pathological grades, and metastasis. Functionally, 64 potential target genes were acquired for further mechanism analysis. Two pathways (p75 neurotrophin receptor and liver kinase B1-mediated signaling pathways), which were likely modulated by miR-191-5p, were regarded to be linked to the deterioration of HCC. Early growth response 1 and UBE2D3 were identified as the most likely targets for miR-191-5p in HCC and were commonly implied in the top enriched pathways and protein-protein network. CONCLUSIONS: In summary, miR-191-5p may function as a tumor promoter miRNA of HCC, and the miR-191-5p inhibitor may contribute to the targeted HCC treatment in the future.

20.
Am J Transl Res ; 11(12): 7233-7254, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31934275

RESUMO

Cyclin-dependent kinase 1 (CDK1) has a unique role in cell cycle regulation, as it is crucial for cell cycle progression and cell division. The aim of the present study was to use a combination of various detection methods to examine the expression and clinical significance of CDK1 in thyroid cancer (THCA). We used in-house tissue microarrays, immunohistochemistry, public RNA-sequencing, gene microarrays, and meta-analyses to conduct a comprehensive analysis of the role of CDK1 in the occurrence and development of THCA. CDK1 protein expression was notably higher in THCA tissues than in non-cancer tissues as evidenced by the in-house tissue microarrays. The expression of CDK1 protein was also significantly higher in pathologic T3-T4 than in T1-T2 samples. The pooled standardized mean difference (SMD) for CDK1 was 0.71 (95% CI, 0.46-0.95) including a total of 931 THCA and 585 non-cancerous thyroid tissue samples. An aggregation of the immunohistochemistry results and the RNA-sequencing/microarray findings gave a pooled SMD for CDK1 expression of 2.13 (95% CI, 1.30-2.96). The final area under curve (AUC) for the summarized receiver operating characteristic (sROC) was 0.7941 using all 1102 cases of THCA and 672 cases of controls. KEGG analysis with the co-expressed genes of CDK1 in THCA demonstrated the top enriched pathways to be the cell cycle, thyroid hormone synthesis, autoimmune thyroid disease, etc. In summary, we reveal the overexpression of CDK1 in THCA based on multiple detection methods that combine independent cohorts. However, further studies are required to elucidate the molecular mechanisms of CDK1 that promotes the biological aggressiveness of THCA cells.

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