RESUMO
Objective: The leptin receptor, encoded by the LEPR gene, is involved in tumorigenesis. A potential functional variant of LEPR, rs1137101 (Gln223Arg), has been extensively investigated for its contribution to the risk of digestive system (DS) cancers, but results remain conflicting rather than conclusive. Here, we performed a case-control study and subsequent meta-analysis to examine the association between rs1137101 and DS cancer risk. Methods: A total of 1,727 patients with cancer (gastric/liver/colorectal: 460/480/787) and 800 healthy controls were recruited. Genotyping of rs1137101 was conducted using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay and confirmed using Sanger sequencing. Twenty-four eligible studies were included in the meta-analysis. Results: After Bonferroni correction, the case-control study revealed that rs1137101 was significantly associated with the risk of liver cancer in the Hubei Chinese population. The meta-analysis suggested that rs1137101 is significantly associated with the risk of overall DS, gastric, and liver cancer in the Chinese population. Conclusion: The LEPR rs1137101 variant may be a genetic biomarker for susceptibility to DS cancers (especially liver and gastric cancer) in the Chinese population.
Assuntos
Neoplasias do Sistema Digestório , Predisposição Genética para Doença , Receptores para Leptina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos de Casos e Controles , China/epidemiologia , Neoplasias do Sistema Digestório/genética , Polimorfismo de Nucleotídeo Único , Receptores para Leptina/genética , Fatores de Risco , População do Leste Asiático/genéticaAssuntos
Interleucinas/genética , Neoplasias Hepáticas/epidemiologia , Neoplasias Pulmonares/epidemiologia , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Neoplasias Gástricas/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Feminino , Humanos , Interleucinas/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Pulmonares/genética , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Neoplasias Gástricas/genética , Adulto Jovem , Interleucina 22RESUMO
AIM: To investigate the regulation of microRNA-124 -(miRNA-124) on NF-κB pathway from H2O2-induced apoptosis and oxidative stress in human lens epithelial cells (hLEC). METHODS: The MTT (3-[4, 5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay was used to detect hLEC -viability. HLECs were divided into Blank, H2O2, mimics (miRNA-124 mimics) + H2O2, NC+ H2O2, pyrrolidine dithiocarbamate (PDTC; NF-κB signaling pathway inhibitor) + H2O2, and inhibitors (miRNA-124 inhibitors) + PDTC + H2O2 groups. Quantitative real-time polymerase chain reaction and Western blot were employed to detect mRNA and protein expressions, Dichloro-dihydro-fluorescein diacetate to measure reactive oxygen species (ROS) production, and AnnexinV-FITC/PI staining to determine cell apoptosis. The mitochondrial membrane potential (MMP) was detected by fluorescence probe JC-1. RESULTS: The H2O2-induced hLEC showed reductions in cell viability with decreased miRNA-124 but increased p-p65 in a dose-/time-dependent manner. Furthermore, ROS production, malondialdehyde content, Bax and Caspase-3 expressions, and cell apoptosis were elevated in H2O2-induced hLEC, whereas the activities of superoxide dismutase and glutathione peroxidase, Bcl-2 expression, MMP, as well as the mitochondrial energy metabolism genes were reduced. Additionally, miRNA-124 mimics and PDTC both decreased the p-p65 and reversed the cytotoxicity in H2O2-induced hLEC. CONCLUSION: MiRNA-124 prevents H2O2-induced oxidative stress and apoptosis in hLEC through suppressing the activation of the NF-κB pathway.