RESUMEN
Tumor necrosis factor receptor-associated factor 5 (TRAF5) has been implicated in the pathogenesis of human malignancies. This work aimed to clarify the role of TRAF5 in lung adenocarcinoma (LUAD) progression. Herein, we uncovered that TRAF5 level was reduced in LUAD tissues. Low TRAF5 expression correlated with dismal prognosis in LUAD patients. Moreover, upregulated TRAF5 impeded cell viability, migration, and invasion, induced apoptosis in vitro, as well as impaired tumorigenicity in vivo. However, depletion of TRAF5 revealed opposing results. Moreover, TRAF5 was identified as the downstream target of methyltransferase-like 3 (METTL3)-elicited N6 -methyladenosine (m6 A) modification. METTL3 stabilized TRAF5 mRNA and positively modulated TRAF5 level. Further, TRAF5 depletion relieved the repressive phenotype caused by METTL3 addition. In addition, it was manifested that the METTL3/TRAF5 axis served as an inhibitor in LUAD through the PI3K/AKT/Nuclear Factor-Kappa B (NF-κB) signaling. Collectively, we propose that METTL3-mediated TRAF5 m6 A modification exerted as a vital tumor inhibitory function in LUAD development. The METTL3/TRAF5 axis may be a critical effector of LUAD progression.
Asunto(s)
Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Humanos , FN-kappa B/genética , FN-kappa B/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Factor 5 Asociado a Receptor de TNF/genética , Factor 5 Asociado a Receptor de TNF/metabolismo , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Metiltransferasas/genética , Metiltransferasas/metabolismo , Transducción de Señal/genética , Metilación , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Adenocarcinoma del Pulmón/genéticaRESUMEN
The increasing number of resistant bacterial strains has raised efforts in developing alternative treatment strategies. Lipase is highly expressed in most bacteria and lipase targeting dyes will be non-sacrificed materials for a sustainable method against microorganism. The combination of chemotherapy and antimicrobial photodynamic inactivation (aPDI) method will be an effective method due to enhanced antibacterial activity. Here we reported the spectroscopic features of five boron dipyrrolylmethene (BODIPY) derivatives with different functional groups for lipase affinity and antibacterial activity. Lipase affinity tests and antibacterial assays were conducted by spectroscopic methods. Adamantane-conjugated BODIPY (BDP-2) was found to be the active compound against E. coli. Next, BDP-2 was brominated, and then assembled with PEG resulting biocompatible BDP2-Br2@mPEG nanoparticles. The MTT assay indicated that BDP2-Br2@mPEG was less toxicity on BGC-823 cancer cells without irradiation. The BDP2-Br2@mPEG can inhibit the proliferation of E. coli and damage the membrane of bacterial cell under green LED light irradiation. The results proved BDP2-Br2@mPEG can be a very promising green LED light driven antibacterial material.
