RESUMO
OBJECTIVE: This study focused on investigating the mechanism in which the KDM5D/E2F1/TNNC1 axis affected hepatocellular carcinoma (HCC) development. METHODS: At first, we determined HCC cell proliferation, migration, invasion, and apoptosis, as well as SOD activity, MDA content, and ROS level. ChIP assay was subsequently conducted to examine H3K4me3 modification in the E2F1 promoter region and the binding of E2F1 to the TNNC1 promoter region after KDM5D overexpression. Meanwhile, we performed western blot for testing KDM5D, H3K4me3, and E2F1 expression after KDM5D overexpression in Huh-7 cells. The binding of transcription factor E2F1 to the TNNC1 promoter region was assessed by dual luciferase reporter gene assay. We further observed the tumor growth ability in nude mice transplanted tumor models. RESULTS: Overexpressed KDM5D suppressed HCC proliferation, migration, and invasion, promoted the apoptosis, suppressed SOD activity, elevated MDA content and ROS level, and promoted ferroptosis. KDM5D suppressed H3K4me3 modification in the E2F1 promoter region and suppressed E2F1 expression in HCC cells. Reduced KDM5D, H3K4me3, and E2F1 expression was found after KDM5D overexpression in Huh-7 cells. Overexpressing E2F1 reversed the inhibitory effects of KDM5D on HCC cell proliferative, migratory, and invasive behaviors. KDM5D repressed TNNC1 transcription by inhibiting E2F1 binding to the TNNC1 promoter. In vivo KDM5D overexpression inhibited HCC development via the E2F1/TNNC1 axis. CONCLUSION: KDM5D inhibits E2F1 expression by suppressing H3K4me3 modification in the E2F1 promoter region, which in turn suppresses the binding of E2F1 to the TNNC1 promoter region, thus leading to the inhibition of HCC development.
RESUMO
INTRODUCTION: Function dyspepsia (FD) may cause patients to suffer from anxiety and depression, and psychosocial disorders would have a significant effect on FD symptoms. AIM: To examine the prevalence of anxiety and depression among function dyspepsia (FD) patients and to identify social factors of anxiety-depression among FD patients. MATERIAL AND METHODS: Patients with FD, who fulfilled the Rome III criteria, were enrolled. All patients were administered a validated Chinese version of the self-rating scale (SDS) and self-rating anxiety scale (SAS), and investigated regarding the patients' social factors. RESULTS: A total of 907 patients were enrolled, including 516 (56.89%) FD patients within anxiety-depression status; SDS mean scores were 51.57 ±8.22; SAS mean scores were 51.04 ±7.53; 52.28% were male and 64.25% were female (χ(2) = 262.54, p < 0.01); 56.16% were aged 18-29 years, 54.15% were aged 30-39 years, 54.77% were aged 40-49 years, 62.02% were aged 50-59 years, 69.23% were aged above 60 years (χ(2) = 18.14, p < 0.01); 67.44% were the retirees; 63.31% were manual workers; 55.10% were soldiers; 43.57% were mental workers; 38.89% were students (χ(2) = 716.53, p < 0.01); 64.20% had junior high school degree or below; 57.36% had high school degrees; 42.03% had college degrees; 44.44% had master's or above degrees (χ(2) = 27.21, p < 0.05); 38.10% were in good health condition; 61.90% were in poor health condition (χ(2) = 7.94, p < 0.01); 20.31% had correlative family history; and 79.69% had no correlative family history (χ(2) = 2.23, p > 0.05). CONCLUSIONS: The FD patients have higher rates of anxiety and depression. Gender, age, occupation, education level, and health condition have a significant effect on anxiety and depression status. Female gender, advanced age, high-stress occupation, lower education level, and poor health condition all are risk factors. Family history has no relationship with anxiety and depression among FD patients.
