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
OBJECTIVE: To investigate the differences in dielectric properties (relative permittivity and conductivity) between the mucosal surface and serosal surface of malignant colorectal tissues, adjacent tissues at 1 cm and 3 cm from the tumor focus and normal colorectal tissues. METHODS: The dielectric properties of the mucosal and serosal surface of malignant colorectal tissues, adjacent tissues (1 cm and 3 cm) and normal colorectal tissues from 39 patients with colorectal cancer were measured with an open-ended coaxial probe within the frequency range of 50 MHz-3 GHz, and the corresponding dielectric properties were analyzed respectively; statistical tests of the data were used to analyze the dielectric properties at 6 specific frequency points. RESULTS: The dielectric properties were significantly higher in the malignant mucosa surface than in the adjacent tissues and normal colorectal tissues at the 6 specific frequency points (P<0.01). The dielectric properties decreased progressively in adjacent tissues at 1 cm and 3 cm and normal mucosa surface. The mucosal and serosal surface of malignant tissues showed significant differences in dielectric properties at 64 MHz, 128 MHz, 298 MHz, 433 MHz, and 915 MHz (P<0.01) but not at 2450 MHz (P>0.01), but such differences were not observed in normal tissues (P>0.01). CONCLUSION: The dielectric properties of the mucosal surface of the mucosal decrease in the order of malignant colorectal tissue, adjacent tissues at 1 cm and 3 cm from the tumor foci and normal colorectal tissues. The dielectric properties are higher in the mucosal surface than in the serosal surface in the malignant tissue, but comparable in normal colorectal tissues.