ABSTRACT
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.
Subject(s)
Adaptor Proteins, Signal Transducing/genetics , Colonic Neoplasms/genetics , MicroRNAs/genetics , Tumor Suppressor Proteins/genetics , cdc42 GTP-Binding Protein/genetics , rho Guanine Nucleotide Dissociation Inhibitor alpha/genetics , Adaptor Proteins, Signal Transducing/metabolism , Animals , Cell Line, Tumor , Colonic Neoplasms/metabolism , Colonic Neoplasms/pathology , Disease Progression , Female , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , HCT116 Cells , HT29 Cells , Humans , Male , Mice, Inbred BALB C , Mice, Nude , Middle Aged , Signal Transduction/genetics , Transplantation, Heterologous , Tumor Suppressor Proteins/metabolism , cdc42 GTP-Binding Protein/metabolism , rho Guanine Nucleotide Dissociation Inhibitor alpha/metabolismABSTRACT
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.
Subject(s)
Biological Products/chemistry , Calcium Carbonate/chemistry , Nacre/chemistry , Nanostructures/chemistry , Calcium Carbonate/chemical synthesis , Mechanical PhenomenaABSTRACT
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.