RESUMO
MicroRNA-125b-1 (miR-125b-1) is a target of a chromosomal translocation t(11;14)(q24;q32) recurrently found in human B-cell precursor acute lymphoblastic leukemia (BCP-ALL). This translocation results in overexpression of miR-125b controlled by immunoglobulin heavy chain gene (IGH) regulatory elements. In addition, we found that six out of twenty-one BCP-ALL patients without t(11;14)(q24;q32) showed overexpression of miR-125b. Interestingly, four out of nine patients with BCR/ABL-positive BCP-ALL and one patient with B-cell lymphoid crisis that had progressed from chronic myelogenous leukemia overexpressed miR-125b. To examine the role of the deregulated expression of miR-125b in the development of B-cell tumor in vivo, we generated transgenic mice mimicking the t(11;14)(q24;q32) (Eµ/miR-125b-TG mice). Eµ/miR-125b-TG mice overexpressed miR-125b driven by IGH enhancer and promoter and developed IgM-negative or IgM-positive lethal B-cell malignancies with clonal proliferation. B cells obtained from the Eµ/miR-125b-TG mice were resistant to apoptosis induced by serum starvation. We identified Trp53inp1, a pro-apoptotic gene induced by cell stress, as a novel target gene of miR-125b in hematopoietic cells in vitro and in vivo. Our results provide direct evidence that miR-125b has important roles in the tumorigenesis of precursor B cells.
Assuntos
Cadeias mu de Imunoglobulina/genética , MicroRNAs/fisiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Animais , Apoptose , Sequência de Bases , Southern Blotting , Cromossomos Humanos Par 11/genética , Cromossomos Humanos Par 14/genética , Citometria de Fluxo , Humanos , Luciferases/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Dados de Sequência Molecular , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patologia , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Homologia de Sequência do Ácido Nucleico , Translocação Genética/genéticaRESUMO
Applications of Cu-HyBrID laser (copper laser with Hydrogen Bromide In Discharge) in Dentistry and AFM (atomic force microscopy) evaluations of dental tissues irradiated by laser are seldom reported in the literature. This work presents an AFM investigation of the cross-section of a cavity generated in human dental enamel by laser thermal evaporation using the Cu-HyBrID laser. The results exposed the structural and morphological differences between the fused and non-fused dental enamel, provide qualitative information about the susceptibility of these tissues to abrasive polishing, and revealed the extension of the thermal damage. Quantitative information concerning the wall thickness and the dimensions of the cross-section of non-fused enamel rod were also obtained.