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1.
Tumour Biol ; 35(11): 11367-73, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25119599

RESUMO

We aimed to study the post-translational regulation of CD151 by the microRNA miR-152. CD151 is highly expressed in gastric cancer (GC) and has been shown to accelerate GC by enhancing invasion and metastasis; however, its regulation is still unclear. Our results showed decreased expression of miR-152 in GC tissue samples and cell lines. In addition, miR-152 complementation significantly inhibits both the proliferation and motility of GC cells. CD151 was found to be a target of miR-152, and overexpression of CD151 attenuated the suppressive effect of miR-152. Our findings highlight an essential role of miR-152 in the regulation of proliferation and motility of GC cells and suggest a potential application of miR-152 in GC treatment.


Assuntos
Movimento Celular , Proliferação de Células , MicroRNAs/genética , Neoplasias Gástricas/patologia , Tetraspanina 24/metabolismo , Apoptose , Western Blotting , Regulação Neoplásica da Expressão Gênica , Humanos , Invasividade Neoplásica , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Tetraspanina 24/genética , Células Tumorais Cultivadas
2.
Mol Biol Rep ; 37(3): 1397-401, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19363658

RESUMO

To study the effects of ovariectomy on tumorigenesis and microsatellite instability (MSI) in rat colon tumors induced by 1,2-dimethylhydrazine, to elucidate the association between postmenopausal ovarian hormones depletion and MSI pathway in colorectal tumorigenesis. Forty female Wistar rats were randomly divided into two groups: Ovariectomized (Ovx) group and Sham-ovariectomized (Sham-Ovx) group. All rats were injected intraperitoneally with 1,2-dimethylhydrazine (DMH) (20 mg/kg b.w) once a week for 20 weeks. Ten weeks after the final DMH injection, all the rats were sacrificed to collect tumors. Microsatellite instability of six microsatellite loci was detected using fluorescent PCR followed by fragment analysis on automatic DNA sequencer with GeneScan 3.7 software. The tumor multiplicity in the OVX group was significantly higher than that in the Sham-OVX group (3.6 +/- 1.4 vs. 2.4 +/- 1.6, P < 0.05). The incidence of MSI-positive tumors in OVX group was higher than that in Sham-OVX group (32.1 vs. 10.8%, P < 0.05).The incidence of tumors showing MSI at multiple loci in OVX group was also higher than that in Sham-OVX group (18.9 vs. 2.7%, P < 0.05). Ovariectomy increased tumor formation and the frequency of MSI in DMH-induced colon tumors. It implied that postmenopausal ovarian hormones depletion might influence colorectal tumorigenesis through MSI pathway.


Assuntos
Neoplasias do Colo/patologia , Hormônios Esteroides Gonadais/deficiência , Instabilidade de Microssatélites , Ovariectomia/efeitos adversos , 1,2-Dimetilidrazina/toxicidade , Animais , Neoplasias do Colo/induzido quimicamente , Neoplasias do Colo/metabolismo , Feminino , Fluorescência , Reação em Cadeia da Polimerase , Ratos , Ratos Wistar
3.
J Huazhong Univ Sci Technolog Med Sci ; 30(1): 69-74, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20155458

RESUMO

We studied the regulatory effects of the estragen receptorbeta (ERbeta) gene on the downstream estrogen signal transfection pathway in colon cancer cells and the possible mechanisms involved. A human ERbeta gene recombinant expression plasmid, pEGFP-C1-ERbeta, was constructed and transfected into the Caco-2 colon cancer cell line, a line with low ERbeta gene expression. The expression of ERbeta mRNA and protein was detected 72 h after transfection. RT-PCR was used to examine the expression levels of the progesterone recepror (PR) gene containing the classic estrogen response element (ERE), the C-fos oncogene containing the AP-1 site (a non-classical ER binding site), the epigenetic modifying genes, such as Dnmt1, Dnmt3a, Dnmt3b, and histone methyltransferase (HMT), and the human mismatch repair gene hMLH1. Methylation-specific PCR was used to detect the changes in the methylated sites of the CpG islands in the promoters of the ERbeta, PR, and C-fos genes. The results indicated that the human ERbeta gene recombinant expression plasmid pEGFP-C1-ERbeta was successfully constructed and transfected into Caco-2 cells. As compared with the control group, the mRNA and protein expression of ERbeta gene was increased significantly 72 h after the transfection of pEGFP-C1-ERbeta into the Caco-2 cells. As compared with the control group, the mRNA expression of the PR, C-fos, Dnmt3a and Dnmt3b genes was increased significantly 72 h after the transfection of pEGFP-C1-ERbeta into the Caco-2 cells, but the mRNA expression of the Dnmt1, HMT, and hMLH1 genes decreased significantly (P<0.05). As compared with the control group, different degrees of demethylation occurred in the promoters of the ERbeta, progesterone receptor (PR), and C-fos oncogene 72 h after the transfection of pEGFP-C1-ERbeta into the Caco-2 cells. The methylation index of the estrogen signal transfection pathway in Caco-2 cells was decreased significantly following the expression restoration of ERbeta gene (P<0.05). It is concluded that the restoration or up-regulation of the ERbeta gene in Caco-2 cells may significantly activate the expression of the related target genes in the downstream estrogen signal transfection pathway and may result in the demethylation changes of the pathway. During the process, the expression level and activity of the epigenetic modifying genes and the human mismatch repair gene have changed simultaneously. The regulatory effect of the ERbeta gene on the estrogen signal transfection pathway to a certain extent partly involves demethylation.


Assuntos
Epigênese Genética , Receptor beta de Estrogênio/genética , Estrogênios/metabolismo , Transdução de Sinais , Células CACO-2 , Metilação de DNA , Reparo de Erro de Pareamento de DNA , Receptor beta de Estrogênio/metabolismo , Humanos , Regiões Promotoras Genéticas , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores de Progesterona/genética , Transfecção
4.
Medicine (Baltimore) ; 95(5): e2129, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26844449

RESUMO

This meta-analysis was designed to evaluate the diagnostic performance of stool DNA testing for colorectal cancer (CRC) and compare the performance between single-gene and multiple-gene tests.MEDLINE, Cochrane, EMBASE databases were searched using keywords colorectal cancers, stool/fecal, sensitivity, specificity, DNA, and screening. Sensitivity analysis, quality assessments, and performance bias were performed for the included studies.Fifty-three studies were included in the analysis with a total sample size of 7524 patients. The studies were heterogeneous with regard to the genes being analyzed for fecal genetic biomarkers of CRC, as well as the laboratory methods being used for each assay. The sensitivity of the different assays ranged from 2% to 100% and the specificity ranged from 81% to 100%. The meta-analysis found that the pooled sensitivities for single- and multigene assays were 48.0% and 77.8%, respectively, while the pooled specificities were 97.0% and 92.7%. Receiver operator curves and diagnostic odds ratios showed no significant difference between both tests with regard to sensitivity or specificity.This meta-analysis revealed that using assays that evaluated multiple genes compared with single-gene assays did not increase the sensitivity or specificity of stool DNA testing in detecting CRC.


Assuntos
Neoplasias Colorretais/diagnóstico , DNA/análise , Fezes/química , Genes Neoplásicos , Programas de Rastreamento/métodos , Humanos , Curva ROC
5.
Oncol Lett ; 4(4): 755-758, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23205096

RESUMO

Mast cells (MCs) and regulatory T cells (Tregs) are the important components of the inflammatory infiltrating leukocytes in most malignant tumors. Our study was designed to investigate the infiltrating correlation between MCs and Tregs and clarify their prognostic significance in gastric cancer (GC). A total of 60 fresh GC tissues were collected and tumor-infiltrating leukocytes were isolated by gradient centrifugation. Tryptase and Foxp3 were used as markers for MCs and Tregs, respectively. The expression of tryptase and Foxp3 was determined in tumor-infiltrating leukocytes using flow cytometry. The expression of tryptase and Foxp3 were positively correlated. The increased infiltration of MCs correlated significantly with advanced stage of GC. The infiltration of MCs into the tumor may increase the number of Tregs. Tryptase is a promising marker to stratify GC patients into different risk groups.

6.
Artigo em Chinês | WPRIM | ID: wpr-341122

RESUMO

We studied the regulatory effects of the estragen receptorβ(ERβ)gene on the downstream estrogen signal transfection pathway in colon cancer cells and the possible mechanisms involved.A human ERβ gene recombinant expression plasmid,pEGFP-C1-ERβ,was constructed and transfected into the Caco-2 colon cancer cell line,a line with low ERβ gene expression.The expression of ERβmRNA and protein was detected 72 h after transfection.RT-PCR was used to examine the expression levels of the progesterone recepror(PR)gene containing the classic estrogen response element(ERE),the C-fos oncogene containing the AP-1 site(a non-classical ER binding site),the epigenetic modifying genes,such as Dnmt1,Dnmt3a,Dnmt3b,and histone methyltransferase(HMT),and the human mismatch repair gene hMLH1.Methylation-specific PCR was used to detect the changes in the methylated sites of the CpG islands in the promoters of the ERβ,PR,and C-fos genes.The results indicated that the human ERβ gene recombinant expression plasmid pEGFP-C1-ERβ was successfully constructed and transfected into Caco-2 cells.As compared with the control group,the mRNA and protein expression of ERβ gene was increased significantly 72 h after the transfection of pEGFP-C1-ERβ into the Caco-2 cells.As compared with the control group,the mRNA expression of the PR,C-fos,Dnmt3a and Dnmt3b genes was increased significantly 72 h after the transfection of pEGFP-C1-ERβ into the Caco-2 cells,but the mRNA expression of the Dnmt1,HMT,and hMLH1 genes decreased significantly(P<0.05).As compared with the control group,different degrees of demethylation occurred in the promoters of the ERβ,progesterone receptor(PR),and C-fos oncogene 72h after the transfection of pEGFP-C1-ERβ into the Caco-2 cells.The methylation index of the estrogen signal transfection pathway in Caco-2 cells was decreased significantly following the expression restoration of ERβ gene(P<0.05).It is concluded that the restoration or up-regulation of the ERβ gene in Caco-2 cells may significantly activate the expression of the related target genes in the downstream estrogen signal transfection pathway and may result in the demethylation changes of the pathway.During the process,the expression level and activity of the epigenetic modifying genes and the human mismatch repair gene have changed simultaneously.The regulatory effect of the ERβ gene on the estrogen signal transfection pathway to a certain extent partly involves demethylation.

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