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
OBJECTIVE: To study the chemical constituents from the tubers of Hemsleya penxianensis. METHODS: The constituents were isolated from the tubers of H. penxianensis and purified by column chromatography, and the structures were identified by spectral analysis and chemical methods. RESULTS: Five compounds were isolated from the tubers of H. penxianensis and the structures were identified as 2β, 3α, 16α, 20, 24-pentahydroxycucurbita-5, 25(E)-diene-11, 22-dione(1), cucurbitacin II a(2), cucurbitacin IIb(3), hemslecins G(4), and jinfushanencins B(5). CONCLUSION: Compound 1 is a new compound.