RESUMO
The extracellular matrix metalloproteinase inducer (EMMPRIN, CD147) is a member of the immunoglobulin family and shows increased expression in tumor cells. We examined the effect of RNAi-mediated EMMPRIN gene silencing induced by lentiviral on the growth and cycle distribution of MCF-7 breast cancer cells. Lentiviral expressing EMMPRIN-short hairpin RNA were packaged to infect MCF-7 cells. The inhibition efficiency of EMMPRIN was validated by real-time fluorescent quantitation polymerase chain reaction and western blotting. The effect of EMMPRIN on cell proliferation ability was detected using the MTT assay and clone formation experiments. Changes in cell cycle were detected by flow cytometry. EMMPRIN-short hairpin RNA-packaged lentiviral significantly down-regulated EMMPRIN mRNA and protein expression, significantly inhibited cell proliferation and in vitro tumorigenicity, and induced cell cycle abnormalities. Cells in the G0/G1 and G2/M phases were increased, while cells in the S phase were decreased after infection of MCF-7 cells for 3 days. The EMMPRIN gene facilitates breast cancer cell malignant proliferation by regulating cell cycle distribution and may be a molecular target for breast cancer gene therapy.
Assuntos
Basigina/genética , Neoplasias da Mama/genética , Ciclo Celular/genética , Inativação Gênica , Proliferação de Células , Feminino , Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Células MCF-7 , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/genética , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismoRESUMO
The endothelial NO synthase (eNOS) enzyme is expressed during the early stages of cardiogenesis and plays an important role in normal heart development. Genetic variations of eNOS G894T have been shown to influence individual susceptibility to some phenotypes of congenital heart disease (CHD) in different populations. We conducted a case-control study comprised of 945 CHD patients and 972 non-CHD individuals in a Chinese population. Two functional single nucleotide polymorphisms (SNPs) (T-786C: rs2070744 and G894T: rs1799983) and one tagging SNP (rs7830) were evaluated in our study, and we assessed their association with the risk of CHD. Compared with the rs7830 CC/AC genotypes, the eNOS rs7830 AA genotype showed a significantly increased risk of CHD (adjusted odds radio (OR) = 1.45, 95% confidence interval (CI = 1.13-1.85). A stratified analysis was performed and showed that the association between the rs7830 AA genotype and CHD risk was stronger in patients with perimembranous ventricular septal defects (adjusted OR = 1.62, 95%CI = 1.20-2.20). Our results suggest that the eNOS rs7830 polymorphism may contribute to the susceptibility of sporadic CHD in a Chinese population.
Assuntos
Estudos de Associação Genética , Predisposição Genética para Doença , Cardiopatias Congênitas/genética , Óxido Nítrico Sintase Tipo III/genética , Povo Asiático , Estudos de Casos e Controles , Pré-Escolar , Feminino , Haplótipos , Cardiopatias Congênitas/patologia , Humanos , Lactente , Masculino , Fatores de RiscoRESUMO
Recent evidence has shown that the microRNA polymorphism may play an important role in the susceptibility to congenital heart disease (CHD). A potentially functional SNP rs4938723 (T>C) in the promoter region of pri-miR-34b/c might affect transcription factor GATA binding and therefore pri-miR-34b/c expression. We genotyped the pri-miR-34b/c polymorphism in a case-control study of 590 patients and 672 controls in a Han Chinese population and assessed the effects of the pri-miR-34b/c polymorphism on CHD susceptibility by TaqMan SNP genotyping assay. There was no association between the pri-miR-34b/c polymorphism and the risk of CHD in both genotype and allelic frequency. In a subsequent analysis of the association between this polymorphism and CHD classification, there was still no significant difference in both genotype and allelic frequency. Our results suggest that the pri-miR-34b/c polymorphism rs4938723 is not associated with susceptibility to sporadic CHD in the Han Chinese population.