RESUMEN
Prostate cancer is a common malignancy of the male reproductive-urinary system. MDM2 is an oncogene, whose expression can be regulated by microRNA (miRNA). The present study investigated the expression and correlation of miRNA-509-5p and MDM2 to determine the mechanism of their function in invasion and migration of prostate cancer cells. RT-PCR was performed to detect the expression of miRNA-509-5p and MDM2 in tumor, tumor-adjacent, and normal tissues, obtained from prostate cancer patients, using the HGC-27 cell line as an in vitro model. Cultured HGC-27 cells were transfected with miRNA-509-5p mimics, miRNA-509-5p inhibitor, and mimic control. Expression levels of miRNA-509-5p and MDM2 were quantified by RT-PCR. Cell proliferation and invasion/migration were examined by the MTT and transwell assays, respectively. MiRNA-509-5p was significantly down-regulated in prostate cancer cells exhibiting high MDM2 mRNA levels. MiRNA mimic transfection elevated miRNA levels and suppressed MDM2 expression. With prolonged incubation time, the proliferation ratio and OD values of miRNA-509-5p mimic transfected cells decreased, along with decrease in cell migration and invasion. These results suggested that miRNA-509-5p negatively regulates MDM2 expression via targeting the 3'-UTR of genes. As a novel tumor suppressor, miRNA-509-5p in prostate cancer HGC-27 cells can suppress MDM2 expression and inhibit cell proliferation, invasion, and migration. Therefore, miRNA-509-5p could be used as a novel therapeutic agent in the treatment of prostate cancer.
Asunto(s)
Movimiento Celular/genética , Regulación Neoplásica de la Expresión Génica , MicroARNs/genética , Neoplasias de la Próstata/genética , Proteínas Proto-Oncogénicas c-mdm2/genética , Regiones no Traducidas 3'/genética , Adulto , Línea Celular Tumoral , Humanos , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Neoplasias de la Próstata/patología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Adulto JovenRESUMEN
We aimed to elucidate the association between connexin 40 (Cx40) genetic polymorphisms and atrial fibrillation (AF) in a Chinese population in Xinjiang comprising Uyghur and Han individuals. We enrolled 275 Uyghur and 305 age- and gender-matched Han subjects, and used polymerase chain reaction to detect single nucleotide polymorphisms (SNPs; -44G/A and +71A/G) in the gene encoding Cx40. A mutation screening was performed by direct sequencing and calculation of genotype and allele frequencies among AF patients and control subjects to determine the relationship between these variants and this condition in Uyghur and Han populations. The two SNPs examined were significantly associated with AF in both ethnic groups. Further analysis showed the SNPs to be in perfect linkage disequilibrium in both AF and control groups among Uyghur and Han individuals. In both populations -44AA genotype and A allele frequencies among AF patients were significantly higher than those in the control group. In addition, under the dominant model (GG vs GA+AA), a significant difference in the distribution of Cx40 -44G/A genotypes was detected between patients and controls. Logistic regression analysis revealed that Cx40 genetic polymorphisms increase AF risk in Uyghur and Han residents of Xinjiang. In conclusion, both the -44G/A and +71A/G variants of the gene encoding this protein are associated with AF in Uyghur and Han populations in northern China.
Asunto(s)
Pueblo Asiatico/genética , Fibrilación Atrial/genética , Conexinas/genética , Etnicidad/genética , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple/genética , Adulto , Anciano , Anciano de 80 o más Años , Alelos , Secuencia de Bases , Estudios de Casos y Controles , China , Electroforesis en Gel de Agar , Femenino , Frecuencia de los Genes/genética , Humanos , Desequilibrio de Ligamiento/genética , Modelos Logísticos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Proteína alfa-5 de Unión ComunicanteRESUMEN
We investigated the association between polymorphisms in the adiponectin gene (APM-1) and atherosclerotic cerebral infarction (ACI) in a Chinese Han population of Hainan Province. Polymerase chain reaction-restriction fragment length polymorphism and gene sequencing were used to analyze the distribution of APM-1 +45T/G and +276G/T genotypes and their alleles in 120 ACI patients and 120 healthy controls. No statistical correlation was found in the frequency and distribution of the genotype 45T/G between the ACI group and the control group. Genotypic frequencies of GG, GT, and TT at the APM-1 +276 locus were 70.0% (84/120), 25.0% (30/120), and 5.0% (6/120), respectively, in the ACI group, while these values were 52.5% (63/120), 37.5% (45/120), and 10.0% (12/120), respectively, in the control group. The frequency of the G allele was 82.5% (198/240) in the ACI group and 71.25% (171/240) in the control group. The T allele frequency was 17.5% (42/240) in the ACI group and 28.75% (69/240) in the control group. Polymorphisms at the APM-1 -276 locus in the case-controlled groups showed significant differences in the genotype distribution and al-lele frequency between the 2 groups (P = 0.041). The occurrence of ACI in the Hainan Chinese Han population may be associated with +276G/T polymorphisms but not with +45T/G polymorphisms in the APM-1 gene.
Asunto(s)
Adiponectina/genética , Infarto Cerebral/genética , Frecuencia de los Genes/genética , Arteriosclerosis Intracraneal/genética , Adiponectina/biosíntesis , Pueblo Asiatico/genética , Secuencia de Bases , Estudios de Casos y Controles , China , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , Polimorfismo de Nucleótido Simple/genética , Análisis de Secuencia de ADNRESUMEN
The TaqI B polymorphism in the cholesterol ester transfer protein (CETP) (B1 and B2 alleles; rs708272) is associated with changes in enzyme activity and lipid concentrations. The B1 allele of the CETP gene is a known independent risk factor for genetic susceptibility to atrial fibrillation (AF); however, little is known about this polymorphism in the minority groups of Xinjiang, China. We examined the role of this polymorphism in AF using two independent case-control studies: the Han population (101 AF patients and 129 control subjects) and the Kazak population (103 AF patients and 101 control subjects). Carriers of the B1B1 genotype were more frequent among AF patients than among controls both in the Han population (34.7 versus 26.4%; χ(2) = 10.686, P = 0.001) and in the Kazak population (53.4 versus 24.8%; χ(2) = 27.802, P < 0.001). The odds ratio (OR) for carriers of the B1B1 genotype to AF susceptibility was 0.187 [95% confidence interval (CI) = 0.071- 0.491] in the Han group and 8.426 (95%CI = 2.295-30.933) in the Kazak population. After adjustment of confounding factors such as gender, age, smoking, alcohol consumption, hypertension, diabetes, as well as serum levels of triglyceride, total cholesterol, and high-density lipoprotein, the difference remained significant in the Han group (P = 0.001; OR = 0.187, 95%CI = 0.071-0.491) and in the Kazak group (P = 0.001; OR = 8.426, 95%CI = 2.295-30.933). The presence of the B1B1 polymorphism of the Taq1B CETP genotype contributes to the development of AF in the Han and Kazak populations in western China (Xinjiang).