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1.
J Cell Biochem ; 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31898364

RESUMO

The study aimed to investigate the expression and function of bladder cancer (BC) long noncoding RNAs (lncRNAs) using a high-throughput platform. High-throughput sequencing was used to compare the expression profiles of lncRNA in BC and adjacent normal tissues. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR), in situ hybridization, gene ontology, and Kyoto Encyclopedia of Genes and Genomes analysis were performed to verify differential expression of lncRNA. The effect of lncRNA overexpression on cellular proliferation, apoptosis, migration, and invasion was analyzed following the transfection of lncRNA overexpressing lentivirus into 5637 and T24 cell lines. The overexpressing cells were subcutaneously injected into nude mice to evaluate their effects on tumor growth. Tumor-associated RNA-binding proteins of lncRNA were analyzed by RNA pull-down combined with mass spectrometry. A total of 93 lncRNA genes were upregulated and 352 lncRNA genes were downregulated in the tissues of patients with BC. Of which, we investigated the function of downregulated lnc-MUC20-9. Overexpression of lnc-MUC20-9 in 5637 and T24 cells resulted in decreased tumor cell viability and cell clones, decreased migration and invasion, and increased apoptosis. Similarly, nude mice bearing lnc-MUC20-9 overexpressing tumor cells exhibited smaller tumor size and volume than that of mice bearing control cells. Mass spectrometry analysis showed that lnc-MUC20-9 binds to ROCK1, an oncogene whose expression was decreased in lnc-MUC20-9 overexpressing cells. The study revealed that lnc-MUC20-9 has the function of inhibiting tumor growth, migration, and invasion. In BC cells, lnc-MUC20-9 binds to ROCK1 and may be involved in lnc-MUC20-9-mediated tumor suppressor function, which might be potential therapeutic targets for BC.

2.
J Cell Biochem ; 2019 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-31886566

RESUMO

Alternative splicing (AS) constitutes a major reason for messenger RNA (mRNA) and protein diversity. Increasing studies have shown a link to splicing dysfunction associated with malignant neoplasia. Systematic analysis of AS events in kidney cancer remains poorly reported. Therefore, we generated AS profiles in 533 kidney renal clear cell carcinoma (KIRC) patients in The Cancer Genome Atlas (TCGA) database using RNA-seq data. Then, prognostic models were developed in a primary cohort (N = 351) and validated in a validation cohort (N = 182). In addition, splicing networks were built by integrating bioinformatics analyses. A total of 11 268 and 8083 AS variants were significantly associated with patient overall survival time in the primary and validation KIRC cohorts, respectively, including STAT1, DAZAP1, IDS, NUDT7, and KLHDC4. The AS events in the primary KIRC cohorts served as candidate AS events to screen the independent risk factors associated with survival in the primary cohort and to develop prognostic models. The area under the curve of the receiver-operator characteristic curve for prognostic prediction in the primary and validation KIRC cohorts was 0.84 and 0.82 at 2500 days of overall survival, respectively. In addition, splicing correlation networks revealed key splicing factors (SFs) in KIRC, such as HNRNPH1, HNRNPU, KHDBS1, KHDBS3, SRSF9, RBMX, SFQ, SRP54, HNRNPA0, and SRSF6. In this study, we analyzed the AS landscape in the TCGA KIRC cohort and detected predictors (prognostic) based on AS variants with high performance for risk stratification of the KIRC cohort and revealed key SFs in splicing networks, which could act as underlying mechanisms.

3.
J Cell Biochem ; 120(3): 3934-3944, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30269365

RESUMO

Nonobstructive azoospermia (NOA) or testicular failure is the most severe form of male infertility. A variety of conditions, both acquired and congenital, can cause azoospermia. However, in a large number of azoospermia patients who are classified as idiopathic cases, the etiology remains poorly understand mainly due to the lack of knowledge of all the genetic causes and molecular mechanisms responsible for spermatogenesis failure. Identification of the key gene modules and pathways-related spermatogenesis failure might help to reveal the mechanisms of idiopathic azoospermia. Therefore, the expression patterns of spermatogenesis-associated genes in NOA were analyzed by weighted gene coexpression network analysis (WGCNA) based on two public microarray data sets (GSE45885 and GSE45887), which included 51 samples and 32,321 genes. We identified a module (turquoise) that was significantly related to the Johnsen score of the testicular samples. In addition, the results of function and pathway enrichment analyses based on the online bioinformatics database Metascape revealed that genes in the turquoise module were mainly related to the process of spermatogenesis and spermatid development. To further identify spermatogenesis-associated genes, a microarray data set (GSE926) of murine testis at different developmental time points was analyzed by WGCNA. The blue module in GSE926 was significantly related to the time of murine testis development. The overlap study and k-core analysis based on protein-protein interaction network revealed that spermatogenesis- and spermatid development-associated genes, including glyceraldehyde-3-phosphate dehydrogenase, ADAM metallopeptidase domain 2, transition protein 1, testis-specific serine kinase 2, transition protein 2, and germ cell-associated 1 (GSG1), were further identified in the selected modules. The expression profile of GSG1 in human testis was chosen for further study using immunochemistry staining. Taken together, these screened gene modules and pathways provided a more detailed genetic and molecular mechanism underlying spermatogenesis failure occurrence and holds promise as potential diagnosis biomarkers and therapeutic targets.

4.
Med Sci Monit ; 24: 1379-1386, 2018 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-29511156

RESUMO

BACKGROUND As a safety and efficacy protocol, oocyte vitrification has been widely used in IVF treatment. The aim of this study was to evaluate the outcome of ICSI-ET utilizing vitrified oocytes with sperm obtained from non-obstructive azoospermia (NOA) patients via micro-TESE. MATERIAL AND METHODS A total of 150 NOA patients underwent micro-TESE. Ten patients were unable to ejaculate and refused to accept TESA at the time of oocyte retrieval; later, these patients underwent TESA. A total of 174 obstructive azoospermia (OA) patients underwent TESA. Vitrified oocytes were used with micro-TESE in 35 cycles (group 1), and TESA in 10 cycles (group 2). Fresh oocytes were used with micro-TESE in 38 cycles (group 3) and TESA in 174 cycles (group 4). RESULTS The overall sperm retrieval rate of the 150 NOA patients was 48.7% (73/150). A total of 257 cycles of ICSI-ET were conducted with testicular spermatozoa; 212 cycles utilized fresh oocytes and 45 cycles utilized vitrified oocytes. No differences were observed with fertilization (73.8%, 77.2%,72.8%, 73.6%), implantation (33.3%, 34.7%, 33.8%, 37.5%), or clinical pregnancy rates (51.4%, 60%, 52.6%, 51.7%) for groups 1 through 4, respectively (P>0.05). Developmental competence was greatest among couples using sperm obtained via TESA rather than micro-TESE, not dependent on whether vitrified or fresh oocytes were utilized. Fertilization, implantation, and clinical pregnancy rates did not differ between using fresh vs. vitrified oocytes, nor did they differ between using testicular sperm derived from men with NOA vs. men with OA. CONCLUSIONS Vitrified oocytes combined with micro-TESE showed similar clinical efficacy when compared with fresh oocytes.


Assuntos
Microdissecção/métodos , Oócitos/fisiologia , Técnicas de Reprodução Assistida , Recuperação Espermática , Vitrificação , Adulto , Azoospermia/terapia , Feminino , Humanos , Masculino , Injeções de Esperma Intracitoplásmicas
5.
Int Immunopharmacol ; 40: 203-210, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27611862

RESUMO

IL-7, acting via IL-7 receptor (IL-7R), plays an important role in tumor progression. Elevated IL-7 expression has been reported to be observed in prostate cancer tissues and closely associated with poor prognosis. However, the biological functions of IL-7 and its receptor in prostate cancer cell invasiveness remain unclear. In our study, we found that the expressions of IL-7 and IL-7R were both upregulated in prostate cancer cells. IL-7 dose-dependently promoted the invasion and migration of prostate cancer cells, whereas knockdown of IL-7R attenuated the effect of IL-7. Further, IL-7/IL-7R axis induced the activation of AKT and NF-κB, whereas blocking of AKT suppressed IL-7-mediated NF-κB activity. Moreover, IL-7/IL-7R axis increased MMP-3 and MMP-7 expression of prostate cancer cells, whereas inhibition of NF-κB as well as MMPs activity suppressed IL-7-mediated cell invasion and migration. Together, these data identify IL-7/IL-7R axis to be involved in prostate cancer cell invasion and migration, probably via activating AKT/NF-κB pathway and upregulating MMP-3 and MMP-7 expression. Therefore, blocking IL-7/IL-7R axis may provide a potential therapeutic strategy to treat prostate cancer.


Assuntos
Interleucina-7/metabolismo , NF-kappa B/metabolismo , Neoplasias da Próstata/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores de Interleucina-7/metabolismo , Linhagem Celular , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Humanos , Masculino , Metaloproteinase 3 da Matriz/metabolismo , Metaloproteinase 7 da Matriz/metabolismo , Invasividade Neoplásica , Neoplasias da Próstata/patologia , Transdução de Sinais
6.
Int J Clin Exp Med ; 8(5): 7794-801, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26221331

RESUMO

Concept mapping is an effective method in teaching and learning, however this strategy has not been evaluated among electrocardiogram (ECG) diagnosis learning. This study explored the use of concept maps to assist ECG study, and sought to analyze whether this method could improve undergraduate students' ECG interpretation skills. There were 126 undergraduate medical students who were randomly selected and assigned to two groups, group A (n = 63) and group B (n = 63). Group A was taught to use concept maps to learn ECG diagnosis, while group B was taught by traditional methods. After the course, all of the students were assessed by having an ECG diagnostic test. Quantitative data which comprised test score and ECG features completion index was compared by using the unpaired Student's t-test between the two groups. Further, a feedback questionnaire on concept maps used was also completed by group A, comments were evaluated by a five-point Likert scale. The test scores of ECGs interpretation was 7.36 ± 1.23 in Group A and 6.12 ± 1.39 in Group B. A significant advantage (P = 0.018) of concept maps was observed in ECG interpretation accuracy. No difference in the average ECG features completion index was observed between Group A (66.75 ± 15.35%) and Group B (62.93 ± 13.17%). According qualitative analysis, majority of students accepted concept maps as a helpful tool. Difficult to learn at the beginning and time consuming are the two problems in using this method, nevertheless most of the students indicated to continue using it. Concept maps could be a useful pedagogical tool in enhancing undergraduate medical students' ECG interpretation skills. Furthermore, students indicated a positive attitude to it, and perceived it as a resource for learning.

7.
Asian Pac J Cancer Prev ; 13(6): 2635-8, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22938433

RESUMO

BACKGROUND: Many studies have investigated the association between glutathione S-transferase T 1 (GSTT1) null genotype and risk of prostate cancer, but the impact of GSTT1 null genotype in Asians is still unclear owing to inconsistencies across results. Thie present meta-analysis aimed to quantify the strength of the association between GSTT1 null genotype and risk of prostate cancer. METHODS: We searched the PubMed, Embase and Wangfang databases for studies of associations between the GSTT1 null genotype and risk of prostate cancer in Asians and estimated summary odds ratio (OR) with their 95% confidence interval (95% CI). RESULTS: A total of 11 case-control studies with 3,118 subjects were included in this meta-analysis, which showed the GSTT1 null genotype to be significantly associated with increased risk of prostate cancer in Asians (random-effects OR = 1.49, 95% CI 1.15-1.92, P = 0.002), also after adjustment for heterogeneity (fixed-effects OR = 1.45, 95% CI 1.23-1.70, P< 0.001). No evidence of publication bias was observed. CONCLUSIONS: This meta-analysis of available data suggested the GSTT1 null genotype does contribute to increased risk of prostate cancer in Asians.


Assuntos
Predisposição Genética para Doença , Glutationa Transferase/genética , Neoplasias da Próstata/genética , Ásia , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , Genótipo , Glutationa Transferase/deficiência , Humanos , Masculino , Fatores de Risco
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