ABSTRACT
The dysregulation of transcription factors is widely associated with tumorigenesis. As the most well-defined transcription factor in multiple types of cancer, c-Myc can transform cells by transactivating various downstream genes. Given that there is no effective way to directly inhibit c-Myc, c-Myc targeting strategies hold great potential for cancer therapy. In this study, we found that WSB1, which has a highly positive correlation with c-Myc in 10 cancer cell lines and clinical samples, is a direct target gene of c-Myc, and can positively regulate c-Myc expression, which forms a feedforward circuit promoting cancer development. RNA sequencing results from Bel-7402 cells confirmed that WSB1 promoted c-Myc expression through the β-catenin pathway. Mechanistically, WSB1 affected β-catenin destruction complex-PPP2CA assembly and E3 ubiquitin ligase adaptor β-TRCP recruitment, which inhibited the ubiquitination of β-catenin and transactivated c-Myc. Of interest, the effect of WSB1 on c-Myc was independent of its E3 ligase activity. Moreover, overexpressing WSB1 in the Bel-7402 xenograft model could further strengthen the tumor-driven effect of c-Myc overexpression. Thus, our findings revealed a novel mechanism involved in tumorigenesis in which the WSB1/c-Myc feedforward circuit played an essential role, highlighting a potential c-Myc intervention strategy in cancer treatment.
ABSTRACT
Objective To observe the protective effect of ghrelin on hippocampal injury induced by global cerebral ischemia/reperfusion (I/R) and explore its effect mechanisms.Methods The male Sprague-Dawley (SD) rats were randomly divided into four groups,namely sham group,I/R group,normal saline (NS)+I/R group and Ghrelin+I/R group,with 42 rats in each group.The model of I/R was reproduced by clipping bilateral carotid artery of rats 15 minutes and then releasing them for 60 minutes.There were no challenges for rats in sham group,just exposed their carotid artery.Ghrelin+I/R group and NS+I/R group were challenged by injecting 1 μ.L ghrelin or NS into lateral ventricle before I/R.Some of brain tissue in the rats was harvested after experiment to determine the levels of malonaldehyele (MDA),myeloperoxidase (MPO) and glutathione (GSH) in hippocampus by using chemical colorimetry and observe infarct sizes and histopathology.Single extracellular neuron discharge in other rats was recorded to observe the activity of glutamic sensitive neurons (Glu-N) and γ-aminobutyric acid (GABA) sensitive neurons (GABA-N) in hippocampus CA1 region of rats suffered I/R.Results Compared with sham group,the levels of MDA and MPO in hippocampus of rats in the I/R group were raised markedly,the level of GSH was decreased significantly,the infarct sizes was increased significantly and pycnosis neurons were increased markedly.All sorts of indexes between NS+I/R group and I/R group showed no significantly statistical significance.Compared with NS+I/R group,the levels of MDA and MPO in hippocampus of rats in the Ghrelin+I/R group were decreased significantly [MDA (nmol/g):16.4 ± 4.2 vs.24.5 ± 6.7,MPO (nmol/g):6.4 ± 1.8 vs.10.2 ± 2.9,both P ＜ 0.05],the activity of GSH was risen remarkably (μmol/g:2.65 ± 0.72 vs.1.66 ± 0.50,P ＜ 0.05),the infarct sizes of hippocampus were reduced markedly [(43.9 ± 9.5)％ vs.(77.0 ± 12.7)％,P ＜ 0.01],the number of pycnosis neuron was reduced markedly (cells:36.2±4.5 vs.47.1 ±6.1,P ＜ 0.01).The results of electrophysiology showed that the discharge frequency of Glu-N and GABA-N in hippocampus CA1 region of rats in I/R group increased markedly as compared with sham group,and no significant difference in the discharge frequency of Glu-N and GABA-N between NS+I/R group and I/R group.Compared with NS+I/R group,injected ghrelin could make the discharge frequency of Glu-N in hippocampus CA1 region of rats decreased markedly (Hz:3.81 ±0.67 vs.4.98±0.33 at ischemia,3.01 ±0.37 vs.3.77 ± 0.41 at reperfusion,both P ＜ 0.05),and the discharge frequency of GABA-N increased markedly (Hz:5.62 ± 0.54 vs.3.62±0.39 at ischemia,4.81±0.48 vs.3.71±0.21 at reperfusion,both P ＜ 0.05).Conclusion Ghrelin might protect hippocampal neuron after I/R iniury,and neuron excitability decrease might be related.
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Objective To study the clinical characteristics of tuberculosis in oral and maxillofacial region,and to provide reference in early diagnosis and early treatment. Methods The clinical data of 132 patients were analyzed retrospectively. ResultsIn all cases, male to female ratio of 1∶1.69, the average age of 38.7 years, the group of 15 ～40year-old had higher incidence. Al1 parts of oral and maxillofacial region could be involved. In all 132 cases,107 cases were treated by surgery and drugs,25 cases by drugs only. Conclusion The local sign of tuberculosis in oral and maxillofacial region was atypical ,so it was likely to misdiagnosis. Definitive diagnosis relied on pathological examination. Operations played an important role in the cases of unifocal lymph nodes tuberculosis,oral mucosal tuberculosis, multifocal concentrated lymph nodes tuberculosis and salivary tuberculosis, while the therapy of multifocal sporadic lymph nodes tuberculosis and osseous tuberculosis should be relied on the medicine.