The relationship between RSUME and small ubiquitin related modifiers of HIF-1α with invasive pituitary adenomas / 中国神经精神疾病杂志

Objective AIM:To study whether the RWD containing sumoylation enhancer (RSUME) enhanced small ubiquitin related modifiers (SUMO) to competitively inhibit Ubiquitin B (UBB)-mediated degradation of hypoxia hypoxia-inducible factor 1α.(HIF-1α) and the invasive pituitary adenomas.Methods The expression of protein and mRNA levels of RSUME,SUMO-1,UBB and HIF-1α were detected by using immunohistochemistry,western blot and qPCR in 38 cases of non-invasive pituitary adenoma,38 cases of invasive pituitary adenomas and 10 cases of normal pituitary capsule.The expression of SUMO-1 was analyzed in different types of pituitary adenomas.Results The protein,and mRNA levels of RSUME,SUMO-HIF-1αwere significantly higher in the invasive pituitary adenomas than in the non-invasive pituitary adenomas and normal pituitary capsule (P＜0.01).The protein and mRNA levels of RSUME,SUMO-HIF-1αwas higher in non-invasive pituitary adenomas than in normal pituitary capsule(P＜0.01).However,the protein levels of UBB-HIF-1α were significantly lower in the invasive pituitary adenomas than in the non-invasive pituitary adenomas and normal pituitary capsule (P＜0.01).The protein of UBB-HIF-1α were lower in non-invasive pituitary adenomas than in normal pituitary capsule (P＜0.01).The expression levels of SUMO were not significantly different among different types of pituitary adenomas (P＞0.05).Conclusion RSUM may increase pituitary adenomas angiogenesis and promote tumor invasion through enhancement of SUMO of HIF-1α which competitively inhibits ubiquitination of HIF-1 α.

RSUME promotes apoptosis of pituitary adenoma cell AtT-20 in mice / 基础医学与临床

Objective To explore the expression and influence of RWD structure small ubiquitin modified enhan-cer (RSUME) and inhibitor of nuclear factor kappa B-alpha (IκB-α) and nuclear factor kappa B-1 (NF-κB1) in pituitary adenomas of mice.Methods Real-time fluorescent quantitative PCR ( q-PCR) was used to detect the level RSUME, IκB-α, NF-κB1 mRNA and Western blot was used to detect RSUME and the nucleoprotein of IκB-α, NF-κB1 changes in the level of protein , flow cytometry was used to detect cell apoptosis .Results In protein level, RSUME and IκB-αexpression reduced ( P<0.05 ) , but NF-κB1 raised after transfection ( P<0.05); The level of RSUME mRNA was obviously lower after transfection than before (P<0.05).The level of IκB-αand NF-κB1 mRNA was not significantly changed; Flow cytometry confirmed cell apoptosis rate increased significantly after transfection.Conclusions RSUME can promote apoptosis of pituitary adenoma cells in mice by NF-κB.

Correlation between RSUME sumoylation and HIF-1α/VEGF pathway in gliomas / 西安交通大学学报(医学版)

Objective To explore the expressions and correlation of RWD containing sumoylation enhancer (RSUME),small ubiquitin-like modifier (SUMO-1),hypoxia inducible factor-1α(HIF-1α)and vascular endothelial growth factor (VEGF)in gliomas of different pathologic grade.Methods We investigated the expression levels of RSUME mRNA,HIF-1α mRNA and VEGF mRNA with reverse transcription-polymerase chain reaction (RT-PCR),and investigated the immunohistochemical staining to determine the expressions of SUMO-1,HIF-1α and VEGF in 63 cases of human gliomas of different pathologic grade and 9 cases of normal brain tissues.We studied its correlation with the pathologic grade and the relationship between the expression of RSUME promoter sumoylation and HIF-1α/VEGF pathway in gliomas.Results There were significant differences (P <0.01)in the expressions of RSUME mRNA,HIF-1αmRNA and VEGF mRNA in glioma tissues.With the increasing degree of pathologic grade in tumor specimens,the expression levels of RSUME mRNA,HIF-1α mRNA and VEGF mRNA increased markedly (P <0.01 ).There was a positive correlation of the expression levels of RSUME mRNA with HIF-1αmRNA and VEGF mRNA.There were significant differences (P <0.01 )in the expressions of SUMO-1,HIF-1αand VEGF in glioma tissues by immunohistochemical staining.With the ascending of pathologic grade of tumor specimens,the expression levels of SUMO-1,HIF-1α and VEGF increased markedly (P < 0.01 ).There was a positive correlation between the expression level of SUMO-1 and HIF-1α(r =0.857,P <0.01).The Kaplan-Meier analysis and Log-rank test showed significant differences in progress free survival (PFS)between the RSUME high-expression and low-expression groups (χ2 =36.032,P <0.01).Conclusion RSUME may enhance HIF-1α/VEGF pathway through sumoylation in gliomas.It implicates that RSUME is related to angiogenesis in gliomas and can promote tumor invasion and progression,indicating that RSUME can be a novel target in gliomas treatment.

Research Progress in molecular mechanisms between RSUME and invasive pituitary adenoma / 中国肿瘤临床

Pituitary adenoma, a benign intracranial tumor, is the third most common brain tumor, second only to glioma and me-ningioma. Pituitary adenoma has been defined as a benign tumor, but some pituitary adenomas can invade the surrounding tissue. This tumor is difficult to resect and can easily recur after surgery. RWD-containing sumoylation enhancer (RSUME) can stabilize the activity of hypoxia-inducible factor-1α and inhibitor kappaB by the small ubiquitin-related modifiers. This phenomenon indicates the impor-tance of RSUME in pituitary adenoma because it promotes the invasiveness of the tumor. However, the correlation between RSUME and the invasion of pituitary adenoma remains unclear. In this study, the roles of RSUME on HIF-1α/VEGF signaling pathway and IκB/NF-κB compomers in the invasiveness of pituitary adenoma were reviewed.