Targeting the COP9 signalosome for cancer therapy

The COP9 signalosome(CSN)is a highly conserved protein complex composed of 8 subunits(CSN1 to CSN8).The individual subunits of the CSN play essential roles in cell proliferation,tumorigenesis,cell cycle regulation,DNA damage repair,angiogenesis,and microenvironmental homeostasis.The CSN complex has an intrinsic metalloprotease that removes the ubiquitin-like activator NEDD8 from cullin-RING ligases(CRLs).Binding of neddylated CRLs to CSN is sensed by CSN4 and communicated to CSN5 with the assistance of CSN6,thus leading to the activation of deneddylase.Therefore,CSN is a crucial regulator at the intersection between neddylation and ubiquitination in cancer progression.Here,we summarize current understanding of the roles of individual CSN subunits in cancer progression.Furthermore,we explain how the CSN affects tumorigenesis through regulating transcription factors and the cell cycle.Finally,we discuss individual CSN subunits as potential therapeutic targets to provide new directions and strategies for cancer therapy.

Analysis of Risk Factors of Postoperative Neurological Complications in Patients with Stanford Type A Aortic Dissection Undergoing Sun’s Procedure

Objective:This study analyzed the risk factors of neurological complications in patients with Stanford type A aortic dissection after Sun’s procedure in a single-center with the purpose of improving the effects.Methods:From January 2019 to December 2020,the clinical data of 480 patients with Stanford type A aortic dissection,who were treated by Sun’s procedure in our center were retrospectively analyzed.Univariate and multivariate logistic regression analyses were used to determine the risk factors of postoperative neurological complications.According to whether there were neurological complications after surgery,they were divided into two groups:the group with complications(n=70)and the group without complications(n=410).The clinical data of the two groups were collected and compared.Results:There were 70 cases of patients with postoperative neurological complications in 480 cases.The incidence rates of temporary neurological dysfunction(TND)and permanent neurological dysfunction(PND)was 11.5%(55/480)and 3.1%(15/480),respectively.Univariate analysis showed that the age(≥70 years),stroke history,femoral artery intubation and cardiopulmonary bypass(CPB)time were associated with postoperative PND(p<0.05).Renal dysfunction,emergency surgery,postoperative hypernatremia,postoperative hyperglycemia,postoperative hypoxemia,postoperative low cardiac output syndrome,and assisted time of suction influenced the occurrence of postoperative TND(p<0.05).Multivariate logistic regression analysis showed that age(≥70 years),stroke history,femoral artery intubation and CPB time were independent risk factors for PND.Renal dysfunction,emergency surgery,postoperative hypernatremia,postoperative hyperglycemia,postoperative hypoxemia,postoperative low cardiac output syndrome,and aspiration time were independent risk factors for TND.Compared with the two groups,the hospitalization time and ICU time of the patients in the neurological complications group were significantly prolonged,and the mortality rate was significantly increased(p<0.05).Conclusion:There are many risk factors for neurological complications in patients with Stanford type A aortic dissection after surgery.With the improvement of surgical techniques,optimization of cerebral perfusion,and interventions for risk factors,Sun’s procedure remains the preferred treatment for Stanford type A aortic dissection.