Background and Aims:Despite advancements in diagnostic and therapeutic strategies,hepatocellular carcinoma(HCC)remains a leading cause of cancer-related mortality.Antioxidant-1(ATOX1)has been implicated in oncogenic p...Background and Aims:Despite advancements in diagnostic and therapeutic strategies,hepatocellular carcinoma(HCC)remains a leading cause of cancer-related mortality.Antioxidant-1(ATOX1)has been implicated in oncogenic processes across various cancer types;however,its specific role in HCC remains unclear.This study aimed to investigate the function of ATOX1 and its underlying molecular mechanisms in HCC.Methods:Immunohistochemical analysis was conducted to assess ATOX1 expression in HCC tissues.Cell Counting Kit-8,colony formation,Transwell migration,flow cytometry,and reactive oxygen species(ROS)assays were employed to evaluate the malignant behaviors of tumor cells.A xenograft mouse model was employed to assess the effects of ATOX1 knockdown on tumor growth in vivo.DCAC50 treatment was performed to inhibit the copper transport function of ATOX1.RNA sequencing was conducted to explore the potential molecular mechanisms of ATOX1 in HCC.Results:ATOX1 expression was significantly elevated in HCC tumor tissues.ATOX1 promoted cell proliferation,colony formation,and migration.Knockdown of ATOX1 suppressed tumor growth in vivo.Mechanistically,ATOX1 activated c-Myb,and thus enhanced the malignant phenotype of HCC cells via activation of the PI3K/AKT signaling pathway.Additionally,ATOX1 reduced intracellular copper accumulation and inhibited ROS production and apoptosis.Inhibition of ATOX1 by DCAC50 decreased cell proliferation while increasing ROS levels and apoptosis in HCC cells.Notably,acetylcysteine reversed the reduction in c-Myb expression induced by ATOX1 knockdown.Conclusions:ATOX1 may promote HCC carcinogenesis through the activation of the c-Myb/PI3K/AKT pathway and the inhibition of copper accumulation and oxidative stress.展开更多
Brain tissue requires high amounts of copper(Cu)for its key physiological processes,such as energy production,neurotransmitter synthesis,maturation of neuropeptides,myelination,synaptic plasticity,and radical scavengi...Brain tissue requires high amounts of copper(Cu)for its key physiological processes,such as energy production,neurotransmitter synthesis,maturation of neuropeptides,myelination,synaptic plasticity,and radical scavenging.The requirements for Cu in the brain vary depending on specific brain regions,cell types,organism age,and nutritional status.Cu imbalances cause or contribute to several life-threatening neurologic disorders including Menkes disease,Wilson disease,Alzheimer’s disease,Parkinson’s disease,and others.Despite the well-established role of Cu homeostasis in brain development and function,the mechanisms that govern Cu delivery to the brain are not well defined.This review summarizes available information on Cu transfer through the brain barriers and discusses issues that require further research.展开更多
基金supported by grants from the Nature Science Foundation of China(no.81650014)Digestive Medical Coordinated Development Center of Beijing Municipal Administration of Hospitals(no.XXZ0501,XXX0101,XXT03).
文摘Background and Aims:Despite advancements in diagnostic and therapeutic strategies,hepatocellular carcinoma(HCC)remains a leading cause of cancer-related mortality.Antioxidant-1(ATOX1)has been implicated in oncogenic processes across various cancer types;however,its specific role in HCC remains unclear.This study aimed to investigate the function of ATOX1 and its underlying molecular mechanisms in HCC.Methods:Immunohistochemical analysis was conducted to assess ATOX1 expression in HCC tissues.Cell Counting Kit-8,colony formation,Transwell migration,flow cytometry,and reactive oxygen species(ROS)assays were employed to evaluate the malignant behaviors of tumor cells.A xenograft mouse model was employed to assess the effects of ATOX1 knockdown on tumor growth in vivo.DCAC50 treatment was performed to inhibit the copper transport function of ATOX1.RNA sequencing was conducted to explore the potential molecular mechanisms of ATOX1 in HCC.Results:ATOX1 expression was significantly elevated in HCC tumor tissues.ATOX1 promoted cell proliferation,colony formation,and migration.Knockdown of ATOX1 suppressed tumor growth in vivo.Mechanistically,ATOX1 activated c-Myb,and thus enhanced the malignant phenotype of HCC cells via activation of the PI3K/AKT signaling pathway.Additionally,ATOX1 reduced intracellular copper accumulation and inhibited ROS production and apoptosis.Inhibition of ATOX1 by DCAC50 decreased cell proliferation while increasing ROS levels and apoptosis in HCC cells.Notably,acetylcysteine reversed the reduction in c-Myb expression induced by ATOX1 knockdown.Conclusions:ATOX1 may promote HCC carcinogenesis through the activation of the c-Myb/PI3K/AKT pathway and the inhibition of copper accumulation and oxidative stress.
基金supported by the National Institute of Health grant R01 GM101502(to SL).
文摘Brain tissue requires high amounts of copper(Cu)for its key physiological processes,such as energy production,neurotransmitter synthesis,maturation of neuropeptides,myelination,synaptic plasticity,and radical scavenging.The requirements for Cu in the brain vary depending on specific brain regions,cell types,organism age,and nutritional status.Cu imbalances cause or contribute to several life-threatening neurologic disorders including Menkes disease,Wilson disease,Alzheimer’s disease,Parkinson’s disease,and others.Despite the well-established role of Cu homeostasis in brain development and function,the mechanisms that govern Cu delivery to the brain are not well defined.This review summarizes available information on Cu transfer through the brain barriers and discusses issues that require further research.
