RESUMEN
The goal of present study was to investigate the relationship between polymorphisms of TGF-ß1 and familial aggregation of liver cancer in Guangxi Zhuang, Han, and Yao populations. We conducted a population-based case-control family study of liver cancer in Guanxi, China. A total of 214 individuals from 37 case families were surveyed for polymorphisms in TGF-ß1. We genotyped six functional TGF-ß1 polymorphisms: rs1800469, rs2241715, rs2241716, rs11466345, rs8105161, and rs747857. Levels of TGF-ß1, hepatitis B surface antigen, and anti-hepatitis C virus in all serum samples were detected using the enzyme-linked immunoassay method, and presence of hepatitis B virus (HBV) DNA was determined using polymerase chain reaction amplification. A standardized questionnaire was used to collect information from subjects, including alcohol consumption, smoking, eating, and water drinking habits. The results were compared with those from 214 control individuals. The results showed that the TGF-ß1 genotypes rs1800469, rs2241715, rs2241715, and rs8105161 were more frequent in patients than in controls. The risk factors for familial aggregation of liver cancer in Guangxi were determined, from high to low, to be: drinking sugared beverages > alcohol consumption > HBV DNA-positive > rs1800469 TT homozygous genotype > rs2241715 TT homozygous genotype. The results suggested that TGF-ß1 rs1800469 TT and rs2241715 TT homozygote genotypes represent the genetic factors underlying familial clustering of liver cancer in Guangxi, and that drinking water use, alcohol consumption, and testing positive for HBV DNA are the main environmental factors contributing to familial aggregation of liver cancer in Guangxi.
Asunto(s)
Predisposición Genética a la Enfermedad , Neoplasias Hepáticas/genética , Polimorfismo de Nucleótido Simple/genética , Factor de Crecimiento Transformador beta1/genética , Estudios de Casos y Controles , China/epidemiología , ADN Viral/genética , Familia , Estudios de Asociación Genética , Hepatitis B/genética , Humanos , Incidencia , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/epidemiología , Modelos Logísticos , Factores de Riesgo , Factor de Crecimiento Transformador beta1/sangreRESUMEN
OBJECTIVE: MicroRNAs (miRNAs) play a role in the pathogenesis of hepatocellular carcinoma (HCC). This study was designed to elucidate the role of microRNA-31 (miR-31) in HCC. MATERIALS AND METHODS: HuH7 cell lines were transfected with miR-31 mimic or miR-31 inhibitor to investigate the role of miR-31 in regulating interferon regulatory factor-1 (IRF-1). The mRNA and protein expression levels of IRF-1 were quantitatively detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blot, respectively. Subsequently, Dual-Luciferase reporter assay was also performed. RESULTS: The expression level of miR-31 was significantly up-regulated in HuH7 cells when compared with that in primary human hepatocytes (hHC). Dual-Luciferase reporter assay indicated that IRF-1 was the direct target of miR-31. The expression levels of IRF-1 were decreased in HuH7 and HepG2 cell lines. IRF-1 was negatively correlated with miR-31 in HCC tissues and paired adjacent tissues. The expression level of miR-31 was inversely correlated with IRF-1. MiR-31 inhibitor up-regulated the expression levels of IRF-1 in HuH7 cells, whereas miR-31 mimic down-regulated the expression levels of IRF-1. Furthermore, the miR-31 mimic repressed IRF-1-3'UTR reporter activity, whereas the miR-31 inhibitor enhanced IRF-1-3'UTR reporter activity depending on the concentration of miR-31 mimic and miR-31 inhibitor. CONCLUSIONS: These results indicated that miR-31 can regulate the expression level of IRF-1 in HCC, which probably provided novel theoretical evidence for the application of target miR-31 treatment of HCC.