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1.
Mol Ther ; 27(6): 1153-1165, 2019 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-31010740

RESUMO

E2F transcription factors (E2Fs), a group of genes that encode a family of transcription factors, have been identified as being involved in the tumor progression of various cancer types. Increasing experimental evidence indicates that E2Fs are implicated in breast cancer tumorigenesis. However, the diverse expression patterns and prognostic values of eight E2Fs have yet to be analyzed. Herein we investigated the transcriptional and survival data of E2Fs in patients with breast cancer from the Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), Kaplan-Meier Plotter, and cBioPortal databases. We found that the expression levels of E2F1-3 and 5-8 were higher in breast cancer tissues than in normal breast tissues, whereas the expression level of E2F4 was lower in the former than in the latter. The expression levels of E2F2, 5, 7, and 8 were correlated with advanced tumor stage. Survival analysis using the Kaplan-Meier Plotter database revealed that the high transcription levels of E2F1-3, 5, 7, and 8 were associated with low relapse-free survival in all of the patients with breast cancer. Conversely, high E2F4 and E2F6 levels predicted high relapse-free survival in these patients. This study implied that E2F1-3, 5, 7, and 8 are potential targets of precision therapy for patients with breast cancer and that E2F4 and 6 are new biomarkers for the prognosis of breast cancer.

2.
Aging (Albany NY) ; 10(5): 973-987, 2018 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-29754146

RESUMO

E2F is a group of genes that encode a family of transcription factors (TFs) in higher eukaryotes and participate in cell cycle regulation and DNA synthesis in mammalian cells. Evidence from cell lines, mouse models, and human tissues indicates that TFs are implicated in lung cancer (LC) tumorigenesis. However, the diverse expression patterns and prognostic values of eight E2Fs have yet to be elucidated. In the current study, we examined the transcriptional and survival data of E2Fs in patients with LC from ONCOMINE, GEPIA, Kaplan-Meier Plotter, and cBioPortal databases. We found that the expression levels of E2F1/2/3/5/6/7/8 were higher in lung adenocarcinoma and squamous cell lung carcinoma tissues than in lung tissues, whereas the expression level of E2F4 was lower in the former than in the latter. The expression levels of E2F2/4/5/7/8 were correlated with advanced tumor stage. Survival analysis using the Kaplan-Meier Plotter database revealed that the high transcription levels of E2F1/2/4/5/7/8 were associated with low relapse-free survival (RFS) in all of the patients with LC. Conversely, high E2F3/6 levels predicted high RFS in these patients. This study implied that E2F3/6/7 are potential targets of precision therapy for patients with LC and that E2F1/2/4/5/8 are new biomarkers for the prognosis of LC.

3.
Curr Pharm Des ; 23(39): 5973-5982, 2018 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-28714412

RESUMO

MicroRNAs are small non-coding RNAs with regulatory biological activity, by modulating target genes on epigenetic, transcriptional, post-transciptional and translational levels. Hundreds of reports indicated that miRNAs play important roles in non-small cell lung cancer (NSCLC). Actually, microRNAs are both regulation targets and regulators targeting effector genes. This article reviewed multifaceted role of microRNAs associated to NSCLC, not only targeting to but also targeted by tumor related genes, to help us understand microRNAs related complex regulation networks. Aberrant expressed micoRNAs and their targets were summarized; the statistical results showed that several microRNAs may play key roles by targeting multiple tumor associated targets. On the other hand, Oncogenes and tumor repressors represented by PTEN were also shown to be the most popular targets of microRNAs. Additionally, ZEB1/2 may be a featured pathway in NSCLC, with significant frequency modulated by microRNAs.

4.
Mol Ther Nucleic Acids ; 9: 100-110, 2017 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-29246288

RESUMO

Long noncoding RNAs (lncRNAs) are emerging as important regulators during tumorigenesis by serving as competing endogenous RNAs (ceRNAs). In this study, the qRT-PCR results indicated that the lncRNA protein disulfide isomerase family A member 3 pseudogene 1 (PDIA3P) was overexpressed in oral squamous cell carcinoma (OSCC) and decreased the survival rate of OSCC patients. CCK-8 and clonal colony formation assays were used to detect the effects of PDIA3P on proliferation. Results revealed that silencing PDIA3P by small interfering RNA (siRNA) inhibited OSCC cell proliferation and repressed tumor growth and reduced the expression of proliferation antigen Ki-67 in vivo. Furthermore, the interaction between PDIA3P and miRNAs was then analyzed by qRT-PCR and luciferase reporter gene assay. We found that PDIA3P negatively regulated miR-185-5p in OSCC cells. Simultaneously, we found that silencing PDIA3P by siRNA suppressed proliferation via miR-185-5p in OSCC cells. Moreover, silencing PDIA3P by siRNA inhibited CCND2 protein (no influence on mRNA levels) expression via miR-185-5p in OSCC cells, and CCND2 facilitated cell proliferation of SCC4 and SCC15 cells induced by sh-PDIA3P#1. Therefore, our study demonstrated that PDIA3P may be a therapeutic target for the treatment of OSCC.

5.
J Huazhong Univ Sci Technolog Med Sci ; 37(6): 849-854, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29270742

RESUMO

The mediastinal lymph node tuberculous abscesses (MLNTAs) are secondary to mediastinal tuberculous lymphadenitis. Surgical excision is often required when cold abscesses form. This study was aimed to examine video-assisted thoracoscopic surgery (VATS) for the treatment of MLNTA. Clinical data of 16 MLNTA patients who were treated in our hospital between December 1, 2013 and December 1, 2015 were retrospectively analyzed. All of the patients underwent the radical debridement and drainage of abscesses, and intrathoracic lesions were removed by VATS. They were also administered the intensified anti-tuberculosis treatment (ATT), and engaged in normal physical activity and follow-up for 3 to 6 months. The results showed that VATS was successfully attempted in all of the 16 MLNTA patients and they all had good recovery. Two patients developed complications after surgery, with one patient developing recurrent laryngeal nerve injury, and the other reporting poor wound healing. It was concluded that VATS is easy to perform, and safe, and has high rates of success and relatively few side-effects when used to treat MLNTA.


Assuntos
Abscesso/cirurgia , Linfonodos/cirurgia , Mediastino/cirurgia , Mycobacterium tuberculosis/patogenicidade , Cirurgia Torácica Vídeoassistida/métodos , Tuberculose dos Linfonodos/cirurgia , Abscesso/diagnóstico , Abscesso/microbiologia , Abscesso/patologia , Adulto , Feminino , Humanos , Excisão de Linfonodo/instrumentação , Excisão de Linfonodo/métodos , Linfonodos/microbiologia , Linfonodos/patologia , Masculino , Mediastino/microbiologia , Mediastino/patologia , Pessoa de Meia-Idade , Mycobacterium tuberculosis/fisiologia , Cirurgia Torácica Vídeoassistida/instrumentação , Resultado do Tratamento , Tuberculose dos Linfonodos/diagnóstico , Tuberculose dos Linfonodos/microbiologia , Tuberculose dos Linfonodos/patologia
6.
Mol Ther Nucleic Acids ; 6: 140-149, 2017 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-28325280

RESUMO

MicroRNAs (miRNAs) are small noncoding RNAs approximately 20-25 nt in length, which play crucial roles through directly binding to corresponding 3' UTR of targeted mRNAs. It has been reported that miRNAs are involved in numerous of diseases, including cancers. Recently, miR-134 has been identified to dysregulate in handles of human cancers, such as lung cancer, glioma, breast cancer, colorectal cancer, and so on. Increasing evidence indicates that miR-134 is essential for human carcinoma and participates in tumor cell proliferation, apoptosis, invasion and metastasis, drug resistance, as well as cancer diagnosis, treatment, and prognosis. Nevertheless, its roles in human cancer are still ambiguous, and its mechanisms are sophisticated as well, referring to a variety of targets and signal pathways, such as STAT5B, KRAS, MAPK/ERK signal pathway, Notch pathway, etc. Herein, we review the crucial roles of miR-134 in scores of human cancers via analyzing latest investigations, which might provide evidence for cancer diagnose, treatment, prognosis, or further investigations.

7.
BMB Rep ; 47(4): 203-8, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24219865

RESUMO

To gain insights into the effect of MexB gene under the short interfering RNA (siRNA), we synthesized 21 bp siRNA duplexes against the MexB gene. RT-PCR was performed to determine whether the siRNA inhibited the expression of MexB mRNA. Changes in antibiotic susceptibility in response to siRNA were measured by the E-test method. The efficacy of siRNAs was determined in a murine model of chronic P. aeruginosa lung infection. MexB-siRNAs inhibited both mRNA expression and the activity of P. aeruginosa in vitro. In vivo, siRNA was effective in reducing the bacterial load in the model of chronic lung infection and the P. aeruginosa-induced pathological changes. MexB-siRNA treatment enhanced the production of inflammatory cytokines in the early infection stage (P<0.05). Our results suggest that targeting of MexB with siRNA appears to be a novel strategy for treating P. aeruginosa infections.


Assuntos
Proteínas da Membrana Bacteriana Externa/genética , Inativação Gênica , Terapia Genética , Proteínas de Membrana Transportadoras/genética , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/metabolismo , RNA Interferente Pequeno/genética , Animais , Carga Bacteriana , Proteínas da Membrana Bacteriana Externa/metabolismo , Modelos Animais de Doenças , Proteínas de Membrana Transportadoras/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Infecções por Pseudomonas/genética , Infecções por Pseudomonas/imunologia , Infecções por Pseudomonas/microbiologia , Infecções por Pseudomonas/patologia , Infecções por Pseudomonas/terapia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/uso terapêutico
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