RESUMEN
Colorectal cancer (CRC) is one of the leading cancer-related causes of death in the world. Recently, downregulation of microRNA-143 (miR-143) has been observed in CRC tissues. Here in this study, we found that miR-143 expression was downregulated both in CRC patients' blood samples and tumor specimens. MiR-143 expression levels were strongly correlated with clinical stages and lymph node metastasis. Furthermore, insulin-like growth factor-I receptor (IGF-IR), a known oncogene, was a novel direct target of miR-143, whose expression levels were inversely correlated with miR-143 expression in human CRC specimens. Overexpression of miR-143 inhibited cell proliferation, migration, tumor growth and angiogenesis and increased chemosensitivity to oxaliplatin treatment in an IGF-IR-dependent manner. Taken together, these results revealed that miR-143 levels in human blood and tumor tissues are associated with CRC cancer occurrence, metastasis and drug resistance, and miR-143 levels may be used as a new diagnostic marker and therapeutic target for CRC in the future.
Asunto(s)
Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , MicroARNs/metabolismo , Neovascularización Patológica/genética , Compuestos Organoplatinos/uso terapéutico , Animales , Secuencia de Bases , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Movimiento Celular/genética , Proliferación Celular/efectos de los fármacos , Neoplasias Colorrectales/irrigación sanguínea , Neoplasias Colorrectales/genética , Regulación hacia Abajo/efectos de los fármacos , Regulación hacia Abajo/genética , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Ratones , Ratones Desnudos , MicroARNs/genética , Datos de Secuencia Molecular , Neovascularización Patológica/tratamiento farmacológico , Compuestos Organoplatinos/farmacología , Oxaliplatino , Receptor IGF Tipo 1/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
Using Northern blotting, ISH and FISH, we demonstrated miR-34a expresses with aging in the brain of rhesus monkey and rat. Correspondingly, the same trend was found in the primary cultures of cortical neurons. Moreover, we found that induction of miR-34a led to neuronal apoptosis by targeting BCL-2. Our study suggests that miR-34a may play critical roles in neuronal development and ageing.
Asunto(s)
Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Macaca mulatta/genética , MicroARNs/genética , Neuronas/metabolismo , Envejecimiento/genética , Animales , Apoptosis/genética , Células Cultivadas , Femenino , Humanos , Neuronas/citología , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , RatasRESUMEN
MicroRNAs (miRNAs) are important post-transcriptional modulators of gene expression, which have been implicated in many physiological and pathological processes. In this study, we found that miR-219 expressed since early segmentation stages (16s) in spinal cord and mid-, hindbrain in zebrafish using Northern blotting and whole mounts ISH technologies. Moreover, knockdown or overexpression of miR-219 led to specific embryonic defects. Furthermore, TUNEL assay showed that overexpression of miR-219 induced significant cell apoptosis in the head and tail of zebrafish. Our study suggested that miR-219 may play an important role in zebrafish embryonic development.
