RESUMO
Current treatment of intrahepatic cholangiocarcinoma (ICC) remains ineffective because knowledge of ICC carcinogenesis is unclear. Increasing evidence suggests that microRNAs (miRNAs), including miR-191, play an important role in tumorigenesis; but expression and biological functions of miR-191 in ICC remain to be established. This study investigated the functions and underlying mechanisms of miR-191 in ICC. ICC miRNA profiles were generated in five pairs of ICC and matched to normal bile duct tissues by next-generation sequencing technology; ICC miRNA profiles were verified in 18 pairs of ICC tissues and normal bile duct tissues by quantitative RT-PCR. The miR-191-associated mechanisms in ICC were investigated in vitro and in vivo, and clinical outcomes associated with miR-191 were correlated in 84 patients. Our results showed that miR-191 expression was significantly increased in ICC compared with the adjacent normal bile duct tissues (P < 0.001). Overexpression of miR-191 promoted proliferation, invasion, and migration of cholangiocarcinoma cells in vitro and in vivo. The elevated miR-191 expression reduced the expression level of ten-eleven translocation 1 (TET1)-a direct target gene of miR-191 in ICC, which catalyzes demethylation. The reduced TET1 expression level allowed the methylated CpG-rich regions at the p53 gene transcription start site stay methylated, leading to reduced p53 expression level, which compromises p53's anticancer vigor. Finally, miR-191 was found to be an independent risk factor for poor prognosis in patients with ICC (overall survival, hazard ratio = 3.742, 95% confidence interval 2.080-6.733, P < 0.001; disease-free survival, hazard ratio = 2.331, 95% confidence interval 1.346-4.037, P = 0.003). CONCLUSION: Our results suggest that overexpressed miR-191 is associated with ICC progression through the miR-191/TET1/p53 pathway. (Hepatology 2017;66:136-151).
Assuntos
Neoplasias dos Ductos Biliares/genética , Colangiocarcinoma/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Oxigenases de Função Mista/genética , Proteínas Proto-Oncogênicas/genética , Animais , Neoplasias dos Ductos Biliares/patologia , Biópsia por Agulha , Movimento Celular/genética , Proliferação de Células/genética , Colangiocarcinoma/patologia , Estudos de Coortes , Modelos Animais de Doenças , Progressão da Doença , Feminino , Humanos , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Nus , Metástase Neoplásica/genética , Estudos Retrospectivos , Sensibilidade e Especificidade , Transdução de Sinais , Células Tumorais CultivadasRESUMO
Plateau-Rayleigh instability describes the infinite falling stream of fluid breaks into smaller droplets. With the development of nanotechnology, more and more attention is being drawn to Plateau-Rayleigh instability. This surface tension-driven instability performs well in the preparation of the nanoparticles, especially in photonics applications, such as optical micro-resonators in nano-biosensing systems. In this article, we mainly adopt the thermal fluid coupling method. The effect of temperature field on instability is studied with the aid of numerical simulation. In addition, the radius of the inner fluid column, the thickness of the outer fluid, and the temperature gradient are also studied to explore how the factors influence the Plateau-Rayleigh instability. The wavelength of the instability is characterized by droplet diameter, which is formed through the process caused by Plateau-Rayleigh instability.
