RESUMEN
Colorectal cancer (CRC) remains a significant global health issue with high incidence and mortality. Yin Yang 1 (YY1) is a powerful transcription factor that acts dual roles in gene activation and repression. High expression level of YY1 has been reported in CRC, indicating the existence of stable factors of YY1 in CRC cells. We aimed to identify the key molecules and underlying mechanisms responsible for stabilizing YY1 expression in CRC. Mass spectrometry analysis was utilized to identify USP7 as a potential molecule that interacted with YY1. Mechanically, USP7 stabilizes YY1 expression at the protein level by interfering its K63 linkage ubiquitination. YY1 exerts its oncogenic function through transcriptionally activating TRIAP1 but suppressing LC3B. In addition, at the pathological level, there is a positive correlation between the expression of YY1 and the budding of CRC. This study has revealed the intricate interplay between YY1 and USP7 in CRC, suggesting that they could serve as novel therapeutic targets or predictive biomarkers for CRC patients.
Asunto(s)
Proliferación Celular , Neoplasias Colorrectales , Peptidasa Específica de Ubiquitina 7 , Factor de Transcripción YY1 , Humanos , Factor de Transcripción YY1/metabolismo , Factor de Transcripción YY1/genética , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/genética , Peptidasa Específica de Ubiquitina 7/metabolismo , Peptidasa Específica de Ubiquitina 7/genética , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Animales , Metástasis de la Neoplasia , Ratones Desnudos , Ubiquitinación , Ratones , Movimiento Celular , Masculino , Unión ProteicaRESUMEN
Mesoporous bioactive glass nanofibers (MBGNFs) were prepared by a sol-gel/electrospinning technique. Subsequently, a collagen-MBGNF (CM) composite scaffold that simultaneously possessed a macroporous structure and collagen nanofibers was fabricated by a gelation and freeze-drying process. Additionally, immersing the CM scaffold in a simulated body fluid resulted in the formation of bone-like apatite minerals on the surface. The CM scaffold provided a suitable environment for attachment to the cytoskeleton. Based on the measured alkaline phosphatase activity and protein expression levels of osteocalcin and bone sialoprotein, the CM scaffold promoted the differentiation and mineralization of MG63 osteoblast-like cells. In addition, the bone regeneration ability of the CM scaffold was examined using a rat calvarial defect model in vivo. The results revealed that CM is biodegradable and could promote bone regeneration. Therefore, a CM composite scaffold is a potential bone graft for bone tissue engineering applications.
