RESUMO
Discoveries related to an intriguing feature of ubiquitination have prompted a detailed analysis of the ubiquitination patterns in malignant cells. How the "ubiquitinome" is reshaped during multistage carcinogenesis has garnered significant attention. Seminal studies related to the structural and functional characterization of NEDD4 (Neuronal precursor cell-expressed developmentally downregulated-4) have consolidated our understanding at a new level of maturity. Additionally, regulatory roles of non-coding RNAs have further complicated the complex interplay between non-coding RNAs and the members of NEDD4 family. These mechanisms range from the miRNA-mediated targeting of NEDD4 family members to the regulation of transcriptional factors for a broader range of non-coding RNAs. Additionally, the NEDD4-mediated degradation of different proteins is modulated by lncRNAs and circRNAs. The miRNA-mediated targeting of NEDD4 family members is also regulated by circRNAs. Tremendous advancements have been made in the identification of different substrates of NEDD4 family and in the comprehensive analysis of the molecular mechanisms by which various members of NEDD4 family catalyze the ubiquitination of substrates. In this review, we have attempted to summarize the multifunctional roles of the NEDD4 family in cancer biology, and how different non-coding RNAs modulate these NEDD4 family members in the regulation of cancer. Future molecular studies should focus on the investigation of a broader drug design space and expand the scope of accessible targets for the inhibition/prevention of metastasis.
RESUMO
ABSTRACT: The open ductus arteriosus (ODA) is the vessel through which the pathological communication between the aorta and the pulmonary artery persists after birth. Clinical manifestations depend on the size of the duct and the stage of hemodynamic disorders. The course of the defect varies from asymptomatic to extremely severe. With large duct sizes, the latter manifests itself from the first week of life with signs of heart failure. The current research is devoted to the choice of the optimal method of medical and surgical treatment in premature newborns with an unaffected ductus arteriosus. Drug therapy for pulmonary hypertension is recommended only for those patients who have irreversible pulmonary hypertension. Surgical closure of the ODA is recommended for overloads of the left heart or signs of pulmonary hypertension in the presence of blood discharge from left to right and after previously suffered endocarditis. The article analyzes current information about the treatment of premature infants with ODA.
