RESUMEN
Background: Mutations within the myotubularin-related protein 9 gene (MTMR9) have been identified in several families with nonsyndromic intellectual disability (NSID), a generalized neurodevelopmental disorder; however, the relationship between MTMR9 and NSID needs to be verified using a larger sample size. Aim: To explore whether genetic variants in the MTMR9 gene are linked to susceptibility of NSID among the Chinese population. Materials and Methods: Seven single nucleotide polymorphisms (SNPs) of the MTMR9 gene (rs4559208, rs3824211, rs2164272, rs2164273, rs1897951, rs6991606, and rs7815802) were analyzed using family-based association testing among 258 Han Chinese NSID families. Results: Three SNPs of MTMR9 were significantly associated with NSID (z = 2.152, p = 0.031 for rs4559208; z = 2.403, p = 0.016 for rs2164273; and z = 2.758, p = 0.006 for rs7815802). Three alleles of these SNPs were more likely to be transferred from the carrier parents to the affected offspring. Haplotypes constructed using these SNPs also showed a similar transmitting trend (z = 2.505, p = 0.012, χ2(3) = 8.835, and global p = 0.032). Carriers with the G-G-C haplotype showed a higher risk of NSID (odds ratio = 1.46, 95% confidence interval [1.01-2.09], p = 0.04) than others. In silico functional predictions supported an etiological role for these three SNPs in NSID biology. Conclusions: This study provides additional insights into the association of NSID with specific alleles, and haplotypes within the MTMR9 gene. Genotypic analyses of the MTMR9 gene should be considered for patients presenting with NSID of unknown etiology.
Asunto(s)
Discapacidad Intelectual/genética , Proteínas Tirosina Fosfatasas no Receptoras/genética , Adolescente , Adulto , Alelos , Pueblo Asiatico/genética , Estudios de Casos y Controles , Niño , Preescolar , China , Etnicidad/genética , Familia , Femenino , Frecuencia de los Genes/genética , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Genotipo , Haplotipos , Humanos , Masculino , Persona de Mediana Edad , Mutación , Polimorfismo de Nucleótido Simple , Proteínas Tirosina Fosfatasas no Receptoras/metabolismoRESUMEN
OBJECTIVE: The role of miR-365 in cancer cells seemed controversial in previous studies. We thereby in this article aimed to define the role of miR-365 in malignant melanoma (MM) pathogenesis. METHODS: We detected miR-365 expression in malignant melanoma cell lines and then investigated the effects of miR-365 on the metastasis and malignancy of melanoma cells. The correlation between miR-365 level and NRP1 (neuropilin1) was further investigated in clinical malignant melanoma specimens. RESULTS: MiR-365 was strongly down-regulated in malignant melanoma (MM) tissues and cell lines, and its expression levels were associated with lymph node metastasis and clinical stage, as well as overall survival and replase-free survival of MM. We also found that ectopic expression of miR-365 inhibited MM cell proliferation and MM metastasis in vitro and in vivo. We further identified a novel mechanism of miR-365 to suppress MM growth and metastasis. NRP1 was proved to be a direct target of miR-365, using luciferase assay and western blot. NRP1 over-expression in miR-365 expressing cells could rescue invasion and growth defects of miR-365. In addition, miR-365 expression inversely correlated with NRP1 protein levels in MM. CONCLUSION: Our data suggest that miR-365 functions as a tumor suppressor in MM development and progression, and holds promise as a prognostic biomarker and potential therapeutic target for MM.
Asunto(s)
Biomarcadores de Tumor/genética , Melanoma/genética , MicroARNs/biosíntesis , Neuropilina-1/biosíntesis , Animales , Biomarcadores de Tumor/biosíntesis , Proliferación Celular/genética , Supervivencia sin Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Estimación de Kaplan-Meier , Metástasis Linfática , Masculino , Melanoma/patología , Ratones , MicroARNs/genética , Invasividad Neoplásica/genética , Metástasis de la Neoplasia , Neuropilina-1/genética , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
OBJECTIVE: The role of miR-365 in cancer cells seemed controversial in previous studies. We thereby in this article aimed to define the role of miR-365 in malignant melanoma (MM) pathogenesis. METHODS: We detected miR-365 expression in malignant melanoma cell lines and then investigated the effects of miR-365 on the metastasis and malignancy of melanoma cells. The correlation between miR-365 level and NRP1 (neuropilin1) was further investigated in clinical malignant melanoma specimens. RESULTS: MiR-365 was strongly down-regulated in malignant melanoma (MM) tissues and cell lines, and its expression levels were associated with lymph node metastasis and clinical stage, as well as overall survival and replase-free survival of MM. We also found that ectopic expression of miR-365 inhibited MM cell proliferation and MM metastasis in vitro and in vivo. We further identified a novel mechanism of miR-365 to suppress MM growth and metastasis. NRP1 was proved to be a direct target of miR-365, using luciferase assay and western blot. NRP1 over-expression in miR-365 expressing cells could rescue invasion and growth defects of miR-365. In addition, miR-365 expression inversely correlated with NRP1 protein levels in MM. CONCLUSION: Our data suggest that miR-365 functions as a tumor suppressor in MM development and progression, and holds promise as a prognostic biomarker and potential therapeutic target for MM.
Asunto(s)
Movimiento Celular , Proliferación Celular , Melanoma/metabolismo , MicroARNs/metabolismo , Neuropilina-1/metabolismo , Animales , Línea Celular Tumoral , Supervivencia sin Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Estimación de Kaplan-Meier , Metástasis Linfática , Melanoma/genética , Melanoma/mortalidad , Melanoma/secundario , Melanoma/terapia , Ratones Endogámicos BALB C , Ratones Desnudos , MicroARNs/genética , Invasividad Neoplásica , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Neuropilina-1/genética , Interferencia de ARN , Factores de Riesgo , Transducción de Señal , Factores de Tiempo , Transfección , Carga Tumoral , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
The residue of thiabendazole, o-phenylphenol and diphenyl in vegetables and fruits was detected by solid-phase extraction and ultraviolet-spectrophotometry. Samples were extracted under basic conditions with petroleum ether: ethyl acetate (2:1). The analytes were first enriched, purified and separated through a C18 solid-phase extraction column. Thiabendazole, o-phenylphenol and diphenyl in the C18 solid-phase extraction column were eluted with 30% ethanol-acid solution (pH 2.5), 55% methanol -alkaline solution (pH 11.5) and 75% ethanol-acid solution (pH 2.5) respectively ,then detected by ultraviolet-spectrophotometry. The linear ranges were from 1 to 10 microg x mL(-1) with a good linear relationship (r > 0.9998) for thiabendazole, o-phenylphenol and diphenyl. The recovery range was from 72.1% to 103.5%, with the relative standard deviations between 1.2% and 7.7%. The limit of detection (S/N = 3) was 0.09 Mg x mL(-1) (TBZ), 0.5 microg x mL(-1) (OPP) and 0.1 microg x mL(-1) (DP). The method was successfully applied to residues of preservatives in fruits and vegetables. These results indicated that this method is simple, rapid and sensitive for the simultaneous determination requirements of residues in vegetables and fruits.
