RESUMO
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide. MicroRNAs (miRNAs) are important regulators of multiple cellular processes, and the aberrant miRNAs expressions have been observed in different types of cancer including HCC. Their pathysiologic role and their relevance to tumorigenesis are still largely unknown. In this study, we demonstrated the down-regulation of miR-424 in HCC cell lines and tissues by quantitative RT-PCR analyses. Overexpression of miR-424 reduced the HCC cell prolifetation, migration, and invasion. Conversely, inhibiton of miR-424 expression significantly accelerated the cell proliferation, migration, and invasion. In addition, we further identified c-Myb as a functional downstream target of miR-424 by directly targeting the 3'UTR of c-Myb. Furthermore, overexpression of c-Myb impaired miR-424-induced inhibition of proliferation and invasion in HCC cells. Our results demonstrated that miR-424 was involved in tumorigenesis of HCC at least in part by suppression of c-Myb.
Assuntos
Carcinoma Hepatocelular/genética , Movimento Celular/genética , Regulação Neoplásica da Expressão Gênica , Genes myb , Neoplasias Hepáticas/genética , MicroRNAs/genética , Regiões 3' não Traduzidas , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células , Transformação Celular Neoplásica/genética , Regulação para Baixo , Humanos , Neoplasias Hepáticas/patologia , RNA Mensageiro/genéticaRESUMO
CONCLUSION: A better animal model of autoimmune inner ear disease (AIED) in Sprague-Dawley rats has been developed by combination with high dose of pertussis toxin. This study also indicated that inner ear-specific antigens can be involved in autoimmune reactions. Cell-mediated immune injury can play an important role in the induction of AIED, at least in the earlier stage. OBJECTIVES: The purpose of this study was to develop a more suitable rat model that demonstrated closer resemblance to the pathophysiological process in AIED. METHODS: Ninety-six female Sprague-Dawley rats were divided into four groups. They were subcutaneously immunized with crude inner ear antigen/complete Freund's adjuvant (CIEAg/CFA), or intraperitoneal injection of 500 ng pertussis toxin (PT), or injection of CIEAg/CFA+PT, or phosphate-buffered saline (PBS) alone. The auditory function, histopathology of the inner ear, and autoantibodies were examined. RESULTS: Significant differences in the time course of auditory brainstem response (ABR) threshold and mean score of cellular infiltration were demonstrated in the CIEAg/CFA+PT group of animals. Missing hair cells, degeneration of the spiral ganglion cells, endolymphatic hydrops, and autoantibodies were all noted after immunization. There were no significant differences in ABR threshold or histopathology in any other group of animals.
