RESUMO
Wilms tumor gene on the X chromosome (WTX) is a putative tumor suppressor gene in Wilms tumor, but its expression and functions in other tumors are unclear. Colorectal cancer (CRC) is the third leading cause of cancer-related deaths in women and the second leading cause in men in the United States. We demonstrated that WTX frequently lost in CRC which was highly correlated with cell proliferation, tumor invasion and metastasis. Mechanistically, WTX loss disrupts the interaction between RhoGDIα and CDC42 by losing of the binding with RhoGDIα and triggers the activation of CDC42 and its downstream cascades, which promotes CRC development and liver metastasis. The aberrant upregulation of miR-20a/miR-106a were identified as the reason of WTX loss in CRC both in vivo and in vitro. These study defined the mechanism how miR-20a/miR-106a-mediated WTX loss regulates CRC progression and metastasis, and provided a potential therapeutic target for preventing CRC progression.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Neoplasias do Colo/genética , MicroRNAs/genética , Proteínas Supressoras de Tumor/genética , Proteína cdc42 de Ligação ao GTP/genética , Inibidor alfa de Dissociação do Nucleotídeo Guanina rho/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Linhagem Celular Tumoral , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Progressão da Doença , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Células HCT116 , Células HT29 , Humanos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Transdução de Sinais/genética , Transplante Heterólogo , Proteínas Supressoras de Tumor/metabolismo , Proteína cdc42 de Ligação ao GTP/metabolismo , Inibidor alfa de Dissociação do Nucleotídeo Guanina rho/metabolismoRESUMO
Single-crystalline CaCO(3) nanotablets are synthesized in large quantities through oriented attachment of pristine nanoparticles. The prepared nanotablets can serve as genuine building blocks for the construction of nacreous inorganic-organic hybrids, through which freestanding films and monoliths with tunable composition and mechanical properties are fabricated. These newly available CaCO(3) crystal tablets may also serve as a starting platform for future CaCO(3) research.
Assuntos
Produtos Biológicos/química , Carbonato de Cálcio/química , Nácar/química , Nanoestruturas/química , Carbonato de Cálcio/síntese química , Fenômenos MecânicosRESUMO
Calcium carbonate (CaCO(3)) is one of the most abundant and important biominerals in nature. Due to its biocompatibility, biodegradability and nontoxicity, CaCO(3) has been investigated extensively in recent years for various fundamental properties and technological applications. Inspired by basic wall structures of cells, we report a protein-assisted approach to synthesize CaCO(3) into a double-shelled structural configuration. Due to varying reactivities of outer and inner shells, the CaCO(3) microcapsules exhibit different sorption capacities and various resultant structures toward different kinds of heavy metal ions, analogical to biologically controlled mineralization (BCM) processes. Surprisingly, three mineralization modes resembling those found in BCM were found with these bacterium-like "CaCO(3) cells". Our investigation of the cytotoxicity (MTT assay protocol) also indicates that the CaCO(3) microcapsules have almost no cytotoxicity against HepG2 cells, and they might be useful for future application of detoxifying heavy metal ions after further study.