ABSTRACT
Oncogenic activation of the NF-κB signaling pathway is common in hepatocellular carcinoma (HCC). However, the molecular mechanisms remain largely unexplored. Previous studies have demonstrated that menin, a tumor suppressor protein, could interact with NF-κB protein and repress p65-mediated transcriptional activation. In the present study, we found that expression of menin was frequently down-regulated in HCC tissues and cells. Furthermore, menin could repress p65 acetylation through recruitment of Sirt1, an enzyme that deacetylases p65 in lysine 310 (K310). Indeed, Sirt1 inhibitor or its specific small interfering RNA abolished the inhibitory roles of menin. Together, these observations suggest that the interaction between menin and Sirt1 is required for the tumor suppressor function of menin in HCC.
Subject(s)
Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/metabolism , Liver Neoplasms/genetics , Liver Neoplasms/metabolism , NF-kappa B/metabolism , Proto-Oncogene Proteins/metabolism , Sirtuin 1/metabolism , Transcriptional Activation , Acetylation , Cell Line, Tumor , Cell Proliferation , Cytokines/metabolism , Gene Expression Regulation, Neoplastic , Humans , Inflammation Mediators/metabolism , Protein Binding , Signal Transduction , Transcription Factor RelA/metabolismABSTRACT
Objective To investigate the relationship between the plasma IL-6,ACE level and DVH parameters radiation pneumonitis,and to evaluate its clinical value on the prediction of radiation pneumonitis.Methods 60 patients with locally advanced non-small cell lung cancer patients with unresectable or unwilling to surgical resection routinely received three-dimensional conformal radiation therapy.Before radiotherapy,radiotherapy beginning 1 week,2 weeks,3 weeks,4 weeks,5 weeks,6 weeks,8 weeks and 12 weeks,enzyme-linked immunosorbent assay (ELISA) was used to detect IL-6 and ACE content.The evaluation of radiation pneumonitis was accordance with the RTOG acute radiation pneumonitis grading standards.The patients with radiation pneumonitis were included in observation group,otherwise as control group.IL-6,ACE and DVH parameters in two groups were analyzed.The DVH parameters includes V20,V20,MLD and NTP.Results Among all the 60 patients,16 cases were diagnosed as radiation pneumonitis,among whom 5 cases occurred in radiotherapy,10 cases occurred within one month after radiotherapy,1 case occurred in two months after radiotherapy,including the 11 cases of grade Ⅱ and the other 5 cases of grade Ⅲ.In the observation group and the control group,expression level of the IL-6 had statistical significance before and after radiotherapy,ACE had significant difference in 2rd,3rd,4th,5th,6th week after radiotherapy (all P ＜ 0.05).V20,V30 and MLD differences were statistically significant between the observation group and control group [(46.2±4.5) ％ vs (30.5±7.5) ％,(37.5±5.6) ％ vs (20.5±5.6) ％,(20.4±2.3) Gy vs (15.5±3.5) Gy,(25.2±8.2) ％ vs (9.9±4.5) ％,all P ＜ 0.05].Conclusion Plasma IL-6,ACE levels,V20,V30,the MLD,and NTP are related to the occurrence of radiation pneumonitis.
