RESUMO
Golgi phosphoprotein 73 (GP73), encoded by GOLM1, is a highly expressed factor in hepatocellular carcinoma (HCC) cells and has been regarded for several years as a remarkable serum biomarker for the diagnosis of HCC. Recently, it was found that upregulation of GP73 promotes cancer metastasis, but the mechanism is complex, and it is even unclear how the gene is transactivated in HCC cells. In this study, it was discovered that c-Myc transactivated GP73 in a mildly hypoxic microenvironment and that the activation of c-Myc upregulated the expression of matrix metalloproteinase-7 (MMP-7). Moreover, it is shown that GP73 interacted with intracellular MMP-7 in the region of the cytoplasmic domain and facilitated the trafficking and secretion of MMP-7, resulting in cell metastasis. This study indicates that GP73 is transactivated by c-Myc and serves as a transporter in the trafficking of intracellular MMP-7 in HCC cells. These findings suggest that GP73 is a potential target for combating metastatic HCC.
RESUMO
For decades, E2F1 has been recognized as a retinoblastoma protein (RB) binding transcription factor that regulates the cell cycle. E2F1 binds preferentially to RB and accelerates the cell cycle in most cancer cells. However, it is thought that E2F1 modulates cell proliferation in other ways as well. Herein, it has been discovered that in pathological tissues derived from hepatocellular carcinoma (HCC) patients, E2F1 correlates positively with IQGAP3 and that both of these factors are highly expressed (N = 164, R = 0.6716). In addition, a high level of E2F1 or IQGAP3 predicted poor survival in HCC patients. Further study determined that E2F1 transactivates IQGAP3, the GTPase binding protein in MHCC-97H cells. Co-immunoprecipitation analysis indicated that IQGAP3 interacts with PKCδ and competitively inhibits the interaction between PKCδ and PKCα, resulting in phosphorylation of PKCα activation and promotion of cell proliferation. This study reveals that highly expressed E2F1 not only transactivates cell-cycle-related factors but also promotes HCC proliferation by activating the phosphorylation of PKCα.
RESUMO
Golgi phosphoprotein 73 (GP73) has been regarded as a novel serum biomarker for the diagnosis of hepatocellular carcinoma (HCC) in recent years. It has been reported that the upregulation of GP73 may promote the carcinogenesis and metastasis of HCC; however, the mechanisms remain poorly understood. In this study, GP73 correlates positively with matrix metalloproteinase-2 (MMP-2) in HCC-related cells and tissues. Further studies indicate that the knockdown of GP73 blocks MMP-2 trafficking and secretion, resulting in cell invasion inhibition. Additionally, the knockdown of GP73 induces the accumulation of intracellular MMP-2, which inhibits the phosphorylation of Src at Y416 and triggers the inhibition of SAPK/JNK and p53-p21 signalling pathways through a negative feedback loop. Finally, the transactivation of MMP2 was inhibited by the reduction in E2F1. This study reveals that GP73 plays functional roles in the trafficking and equilibrium of epithelial-mesenchymal transition (EMT)-related secretory proteins and that GP73 serves as a new potential target for combating the metastasis of HCC.
Assuntos
Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Metaloproteinase 2 da Matriz/genética , Proteínas de Membrana/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Fator de Transcrição E2F1/genética , Transição Epitelial-Mesenquimal/genética , Retroalimentação Fisiológica , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Neoplasias Hepáticas/patologia , Masculino , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Fosforilação/genética , Transporte Proteico/genéticaRESUMO
The objective of the present study was to determine the prevalence of chronic fatigue syndrome (CFS) and its associated factors in middle-school students in Suzhou, China. From September 2010 to January 2011, across-sectional study was conducted in junior- and senior middle-school students aged 10 to 18 years using a battery of confidential questionnaires. Our results indicate that 18,139 completed the questionnaires effectively, of whom 163 (0.9%) met the definition of CFS, with senior high-school students and male students predominating. The prevalence of CFS in the middle-school students increased steadily with age. The main symptoms of CFS in these students included being afraid of going to school, despondency, and irritability in addition to those specified in the Centers for Disease Control and Prevention (CDC). Our study shows that CFS is prevalent among Chinese teenagers, and requiring proper intervention and treatment.
