RESUMO
The JNK signaling pathway plays crucial roles in various physiological processes, including cell proliferation, differentiation, migration, apoptosis, and stress response. Dysregulation of this pathway is closely linked to the onset and progression of numerous major diseases, such as developmental defects and tumors. Identifying and characterizing novel components of the JNK signaling pathway to enhance and refine its network hold significant scientific and clinical importance for the prevention and treatment of associated cancers. This study utilized the model organism Drosophila and employed multidisciplinary approaches encompassing genetics, developmental biology, biochemistry, and molecular biology to investigate the interplay between Tip60 and the JNK signaling pathway, and elucidated its regulatory mechanisms. Our findings suggest that loss of Tip60 acetyltransferase activity results in JNK signaling pathway activation and subsequent induction of JNK-dependent apoptosis. Genetic epistasis analysis reveals that Tip60 acts downstream of JNK, paralleling with the transcription factor FOXO. The biochemical results confirm that Tip60 can bind to FOXO and acetylate it. Introduction of human Tip60 into Drosophila effectively mitigates apoptosis induced by JNK signaling activation, underscoring conserved regulatory role of Tip60 in the JNK signaling pathway from Drosophila to humans. This study further enhances our understanding of the regulatory network of the JNK signaling pathway. By revealing the role and mechanism of Tip60 in JNK-dependent apoptosis, it unveils new insights and potential therapeutic avenues for preventing and treating associated cancers.
Assuntos
Apoptose , Proteínas de Drosophila , Fatores de Transcrição Forkhead , Animais , Proteínas de Drosophila/metabolismo , Proteínas de Drosophila/genética , Fatores de Transcrição Forkhead/metabolismo , Fatores de Transcrição Forkhead/genética , Histona Acetiltransferases/metabolismo , Histona Acetiltransferases/genética , Drosophila/genética , Drosophila/metabolismo , Sistema de Sinalização das MAP Quinases , Humanos , Transdução de Sinais , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/genéticaRESUMO
Hepatocellular carcinoma (HCC) accounts for approximately 90% of all primary liver cancers and is one of the main malignant tumor types globally. It is essential to develop rapid, ultrasensitive, and accurate strategies for the diagnosis and surveillance of HCC. In recent years, aptasensors have attracted particular attention owing to their high sensitivity, excellent selectivity, and low production costs. Optical analysis, as a potential analytical tool, offers the advantages of a wide range of targets, rapid response, and simple instrumentation. In this review, recent progress in several types of optical aptasensors for biomarkers in early diagnosis and prognosis monitoring of HCC is summarized. Furthermore, we evaluate the strengths and limitations of these sensors and discuss the challenges and future perspectives for their use in HCC diagnosis and surveillance.