RESUMEN
BACKGROUND: Cancer stem cells (CSCs) have unique biological characteristics, including tumorigenicity, immortality, and chemoresistance. Colorectal CSCs have been identified and isolated from colorectal cancers by various methods. AKAP12, a scaffolding protein, is considered to act as a potential suppressor in colorectal cancer, but its role in CSCs remains unknown. In this study, we investigated the function of AKAP12 in Colorectal CSCs. METHODS: Herein, Colorectal CSCs were enriched by cell culture with a serum-free medium. CSC-associated characteristics were evaluated by Flow cytometry assay and qPCR. AKAP12 gene expression was regulated by lentiviral transfection assay. The tumorigenicity of AKAP12 in vivo by constructing a tumor xenograft model. The related pathways were explored by qPCR and Western blot. RESULTS: The depletion of AKAP12 reduced colony formation, sphere formation, and expression of stem cell markers in colorectal cancer cells, while its knockdown decreased the volume and weight of tumor xenografts in vivo. AKAP12 expression levels also affected the expression of stemness markers associated with STAT3, potentially via regulating the expression of protein kinase C. CONCLUSION: This study suggests Colorectal CSCs overexpress AKAP12 and maintain stem cell characteristics through the AKAP12/PKC/STAT3 pathway. AKAP12 may be an important therapeutic target for blocking the development of colorectal cancer in the field of cancer stem cells.
Asunto(s)
Neoplasias Colorrectales , Humanos , Línea Celular Tumoral , Neoplasias Colorrectales/patología , Fenotipo , Células Madre Neoplásicas/patología , Proliferación Celular , Proteínas de Ciclo Celular/metabolismo , Proteínas de Anclaje a la Quinasa A/genética , Proteínas de Anclaje a la Quinasa A/metabolismo , Factor de Transcripción STAT3/genéticaRESUMEN
OBJECTIVE: Identification of rare deafness genes for inherited congenital sensorineural hearing impairment remains difficult, because a large variety of genes are implicated. In this study we applied targeted capture and next-generation sequencing to uncover the underlying gene in a three-generation Han family segregating recessive inherited hearing loss and retinitis pigmentosa. METHODS: After excluding mutations in common deafness genes GJB2, SLC26A4 and the mitochondrial gene, genomic DNA of the proband of a Han family was subjected to targeted next-generation sequencing. The candidate mutations were confirmed by Sanger sequencing and subsequently analyzed with in silico tools. RESULTS: An unreported splice site mutation c.3924+1G > C compound with c.6028G > A in the MYO7A gene were detected to cosegregate with the phenotype in this pedigree. Both mutations, located in the evolutionarily conserved FERM domain in myosin VIIA, were predicted to be pathogenic. In this family, profound sensorineural hearing impairment and retinitis pigmentosa without vestibular disorder, constituted the typical Usher syndrome type 2. CONCLUSION: Identification of novel mutation in compound heterozygosity in MYO7A gene revealed the genetic origin of Usher syndrome type 2 in this Han family.
Asunto(s)
Pueblo Asiatico/genética , Familia , Miosinas/genética , Síndromes de Usher/genética , Adolescente , Adulto , Niño , Análisis Mutacional de ADN , Femenino , Heterocigoto , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Masculino , Persona de Mediana Edad , Mutación , Miosina VIIa , Linaje , Fenotipo , Adulto JovenRESUMEN
OBJECTIVE: The aim of this study was to compare serum uric acid values in two ethnically distinct Chinese populations: Uyghur, with a high prevalence of nonalcoholic fatty liver disease, and Han, with a lower prevalence. SUBJECTS AND METHODS: Serum uric acid and several clinical features and laboratory tests relevant to the metabolic syndrome were measured in 4,157 Uyghur and 6,448 Han subjects in a health examination program. The diagnosis of hepatic steatosis was established by abdominal ultrasound examination. RESULTS: The prevalence of nonalcoholic fatty liver disease was 42.3% and 33.3% among Uyghur and Han subjects, respectively. The corresponding prevalence of hyperuricemia was 8.8% and 14.7%. The mean concentration of serum uric acid in Uyghurs also was lower than in Hans (282.75 vs. 310.79 µmol/L; p < 0.01). However, in both populations, the prevalence of nonalcoholic fatty liver disease was increased in association with increasing serum uric acid concentrations, a trend that was more pronounced in Uyghur than in Han subjects (OR 3.279 and 3.230, respectively). Several components of the metabolic syndrome were more pronounced in Uyghurs than in Hans. CONCLUSIONS: Serum uric acid is an independent risk factor in nonalcoholic fatty liver disease in both Uyghurs and Hans, but other risk factors may be more important in the differences in prevalence of the disease between the two ethnic groups.
Asunto(s)
Hígado Graso/etnología , Conducta Alimentaria , Hiperuricemia/etnología , Ácido Úrico/sangre , Adulto , Índice de Masa Corporal , China/epidemiología , China/etnología , Hígado Graso/diagnóstico , Hígado Graso/epidemiología , Femenino , Humanos , Hiperuricemia/diagnóstico , Estilo de Vida , Hígado/diagnóstico por imagen , Masculino , Síndrome Metabólico , Persona de Mediana Edad , Análisis Multivariante , Enfermedad del Hígado Graso no Alcohólico , Prevalencia , Factores de Riesgo , Ultrasonografía , Circunferencia de la CinturaRESUMEN
OBJECTIVE: The aim of this study was to compare serum uric acid values in two ethnically distinct Chinese populations: Uyghur, with a high prevalence of nonalcoholic fatty liver disease, and Han, with a lower prevalence. SUBJECTS AND METHODS: Serum uric acid and several clinical features and laboratory tests relevant to the metabolic syndrome were measured in 4,157 Uyghur and 6,448 Han subjects in a health examination program. The diagnosis of hepatic steatosis was established by abdominal ultrasound examination. RESULTS: The prevalence of nonalcoholic fatty liver disease was 42.3% and 33.3% among Uyghur and Han subjects, respectively. The corresponding prevalence of hyperuricemia was 8.8% and 14.7%. The mean concentration of serum uric acid in Uyghurs also was lower than in Hans (282.75 vs. 310.79 µmol/L; p < 0.01). However, in both populations, the prevalence of nonalcoholic fatty liver disease was increased in association with increasing serum uric acid concentrations, a trend that was more pronounced in Uyghur than in Han subjects (OR 3.279 and 3.230, respectively). Several components of the metabolic syndrome were more pronounced in Uyghurs than in Hans. CONCLUSIONS: Serum uric acid is an independent risk factor in nonalcoholic fatty liver disease in both Uyghurs and Hans, but other risk factors may be more important in the differences in prevalence of the disease between the two ethnic groups.
OBJETIVO: O objetivo deste estudo foi comparar os valores de ácido úrico em duas populações chinesas etnicamente diferentes: Uyghur, com alta prevalência de doença hepática gordurosa não alcoólica, e Han, com prevalência mais baixa. SUJEITOS E MÉTODOS: A concentração sérica de ácido úrico e várias características clínicas e testes laboratoriais relevantes para a síndrome metabólica foram determinados em 4.157 indivíduos Uyghur e 6.448 indivíduos Han submetidos a um programa de checkups. O diagnóstico de esteatose hepática foi estabelecido por ultrassom abdominal. RESULTADOS: A prevalência de doença hepática gordurosa não alcoólica foi de 42,3% e 33,3% entre os indivíduos Uyghur e Han, respectivamente. A prevalência correspondente de hiperuricemia foi de 8,8% e 14,7%. A concentração sérica média de ácido úrico em Uyghurs também foi mais baixa do que em Hans (282,75 contra 310,79 µmol/L; p < 0,01). Entretanto, em ambas as populações, a prevalência de doença hepática gordurosa não alcoólica aumentou com a elevação da concentração sérica de ácido úrico, uma tendência mais pronunciada em Uyghurs do que em Hans (OR 3,279 e 3,230, respectivamente). Vários componentes da síndrome metabólica são mais pronunciados em Uyghurs do que em Hans. CONCLUSÕES: A concentração sérica de ácido úrico é um fator de risco independente para a doença hepática gordurosa não alcoólica tanto em Uyghurs quando em Hans, mas outros fatores de risco podem ser mais importantes nas diferenças na prevalência da doença entre esses dois grupos étnicos.