ABSTRACT
Protein ubiquitination is a common post-translational modification and a critical mechanism for regulating protein stability. This study aimed to explore the role and potential molecular mechanism of ubiquitin-specific peptidase 38 (USP38) in the progression of lung adenocarcinoma (LUAD). USP38 expression was significantly higher in patients with LUAD than in their counterparts, and higher USP38 expression was closely associated with a worse prognosis. USP38 silencing suppresses the proliferation of LUAD cells in vitro and impedes the tumorigenic activity of cells in xenograft mouse models in vivo. Further, we found that USP38 affected the protein stability of transcription factor Krüppel-like factors 5 (KLF5) by inhibiting its degradation. Subsequent mechanistic investigations showed that the N-terminal of USP38 (residues 1-400aa) interacted with residues 1-200aa of KLF5, thereby stabilizing the KLF5 protein by deubiquitination. Moreover, we found that PIAS1-mediated SUMOylation of USP38 was promoted, whereas SENP2-mediated de-SUMOylation of USP38 suppressed the deubiquitination effects of USP38 on KLF5. Additionally, our results demonstrated that KLF5 overexpression restored the suppression of the malignant properties of LUAD cells by USP38 knockdown. SUMOylation of USP38 enhances the deubiquitination and stability of KLF5, thereby augmenting the malignant progression of LUAD.
Subject(s)
Adenocarcinoma of Lung , Transcription Factors , Animals , Humans , Mice , Adenocarcinoma of Lung/genetics , Cell Proliferation/genetics , Kruppel-Like Transcription Factors/genetics , Kruppel-Like Transcription Factors/metabolism , Transcription Factors/metabolism , Ubiquitin-Specific Proteases/genetics , Ubiquitin-Specific Proteases/metabolism , UbiquitinationABSTRACT
Increasing evidence suggests that key cancer-causing driver genes continue to exert a sustained influence on the tumor microenvironment (TME), highlighting the importance of immunotherapeutic targeting of gene mutations in governing tumor progression. TP53 is a prominent tumor suppressor that encodes the p53 protein, which controls the initiation and progression of different tumor types. Wild-type p53 maintains cell homeostasis and genomic instability through complex pathways, and mutant p53 (Mut p53) promotes tumor occurrence and development by regulating the TME. To date, it has been wildly considered that TP53 is able to mediate tumor immune escape. Herein, we summarized the relationship between TP53 gene and tumors, discussed the mechanism of Mut p53 mediated tumor immune escape, and summarized the progress of applying p53 protein in immunotherapy. This study will provide a basic basis for further exploration of therapeutic strategies targeting p53 protein.
Subject(s)
Neoplasms , Tumor Suppressor Protein p53 , Humans , Tumor Suppressor Protein p53/genetics , Genes, p53 , Neoplasms/genetics , Cognition , Genomic Instability , Tumor Microenvironment/geneticsABSTRACT
PURPOSE: The role and mechanism of zinc finger DHHC protein 11B (ZDHHC11B) in lung adenocarcinoma (LUAD) remain unclear. We, thus, analyzed the expression pattern, biological function, and potential mechanism of ZDHHC11B in LUAD. METHODS: The expression level and prognostic value of ZDHHC11B were evaluated based on The Cancer Genome Atlas (TCGA) database and further confirmed in LUAD tissues and cells. The effect of ZDHHC11B on the malignant biological progression of LUAD was evaluated in vitro and in vivo. Gene set enrichment analysis (GSEA) and western blot were used to explore the molecular mechanisms of ZDHHC11B. RESULTS: In vitro, ZDHHC11B inhibited the proliferation, migration, and invasion of LUAD cells and induced the apoptosis of LUAD cells. In addition, ZDHHC11B inhibited the growth of tumors in nude mice. GSEA revealed that ZDHHC11B expression is positively correlated with epithelial-mesenchymal transition (EMT). Western blot analysis demonstrated that molecular markers of EMT were inhibited under ZDHHC11B overexpression conditions. CONCLUSIONS: Our findings indicated that ZDHHC11B plays a significant role in inhibiting tumorigenesis via EMT. In addition, ZDHHC11B may be a candidate molecular target for LUAD treatment.
Subject(s)
Adenocarcinoma of Lung , Epithelial-Mesenchymal Transition , Lung Neoplasms , Animals , Mice , Adenocarcinoma of Lung/genetics , Adenocarcinoma of Lung/pathology , Carcinogenesis/genetics , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Cell Transformation, Neoplastic/genetics , Epithelial-Mesenchymal Transition/genetics , Gene Expression Regulation, Neoplastic , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Mice, Nude , HumansABSTRACT
In this manuscript, dual network self-healing alginate/guar gum hydrogels with polydopamine-type microcapsules from mesoporous silica nanoparticles were facilely prepared through one-pot method. Glutaraldehyde (GA) was used as a crosslinking agent to crosslink guar gum and sodium alginate, respectively. Metal-ligand interactions as reversible non-covalent bonds make the dual network hydrogels have a high degree of self-healing ability, which FeCl3·6H2O was coordinated with sodium alginate and polydopamine on the surface of microcapsules, respectively. The dual network structure significantly enhances the strength of the hydrogels (up to 7.3â¯MPa). It has also proved that these hydrogels exhibit excellent self-healing performance at ambient temperatures, which self-healing efficiency can reach to 95.5%. The obtained self-healing hydrogels have a promising application prospect for the design and synthesis of functional self-healing materials.
Subject(s)
Alginates , Galactans , Hydrogels , Indoles , Mannans , Nanoparticles , Plant Gums , Polymers , Silicon Dioxide , Alginates/chemistry , Galactans/chemistry , Hydrogels/chemistry , Indoles/chemistry , Mannans/chemistry , Nanoparticles/chemistry , Nanoparticles/ultrastructure , Plant Gums/chemistry , Polymers/chemistry , Porosity , Rheology , Silicon Dioxide/chemistry , Spectrum AnalysisABSTRACT
Artificial development of smart materials from agricultural waste or food residues is particularly desirable for green chemistry. In this paper, dual-network self-healing hydrogels were successfully fabricated by using functional microcapsules. These microcapsules were established by biomass porous carbon (PC) after recycling of apple residues. Glutaraldehyde (GA) as the healing agent was embedded in the porous carbon, and the outer surface was coated with polydopamine (PDA). After the microcapsules were added, modifying guar gum-type hydrogels were successfully obtained with dual self-healing performance by the combination of a healing agent and metal-ligand coordination. The self-healing efficiency was about 89.9% from the tension test, and the fracture strength was measured as 7.68 MPa. These results not only highlight a new idea for the utilization of apple residues but also provide a new method for the preparation of excellent self-healing hydrogels.
