RESUMO
In the current study, a typical Sb mine was selected to explore the microbial community composition and assembly driven by the cocontamination of As/Sb with geographic distance. Our results showed that environmental parameters, especially pH, TOC, nitrate, total and bioavailable As/Sb contents largely affected the microbial community diversity and composition. The total and bioavailable As/Sb levels were significantly positively correlated with the relative abundance of Zavarzinella, Thermosporothrix and Holophaga, while the pH presented a significant negative correlation with the three genera, potentially implying they are important taxonomic groups in acid-mining soils. The cooccurrence network analysis indicated the environmental stress dominated by pH and As/Sb co-contamination affected the microbial modularity and interaction. Meanwhile, Homogeneous selection (HoS, 26.4-49.3%), and drift and others (DR, 27.1â¼40.2%) were the most important assembly processes for soil bacterial, and the importance of HoS decreased and the DR increased with geographic distance to the contamination source respectively. Soil pH, nutrient availability, total and bioavailable As/Sb contents significantly affected the HoS and DR processes. This study provides theoretical support for microbial remediation in metal(loid)-contaminated soils.
Assuntos
Arsênio , Microbiota , Poluentes do Solo , Antimônio , Arsênio/análise , Poluentes do Solo/análise , Monitoramento Ambiental , Solo/químicaRESUMO
Dysregulation of microRNAs is a common feature in human cancers, including breast cancer (BC). Here we describe the epigenetic regulation of miR-148a and miR-152 and their impact on BC cells. Due to the hypermethylation of CpG island, the expression levels of both miR-148a and miR-152 (miR-148a/152) are decreased in BC tissues and cells. DNMT1, the DNA methyltransferase 1 for the maintenance methylation, is aberrantly up-regulated in BC and its overexpression is responsible for hypermethylation of miR-148a and miR-152 promoters. Intriguingly, we found that DNMT1 expression, which is one of the targets of miR-148a/152, is inversely correlated with the expression levels of miR-148a/152 in BC tissues. Those results lead us to propose a negative feedback regulatory loop between miR-148a/152 and DNMT1 in BC. More importantly, we demonstrate that IGF-IR and IRS1, often overexpressed in BC, are two novel targets of miR-148a/152. Overexpression of miR-148a or miR-152 significantly inhibits BC cell proliferation, colony formation, and tumor angiogenesis via targeting IGF-IR and IRS1 and suppressing their downstream AKT and MAPK/ERK signaling pathways. Our results suggest a novel miR-148a/152-DNMT1 regulatory circuit and reveal that miR-148a and miR-152 act as tumor suppressors by targeting IGF-IR and IRS1, and that restoration of miR-148a/152 expression may provide a strategy for therapeutic application to treat BC patients.
Assuntos
Transformação Celular Neoplásica/genética , DNA (Citosina-5-)-Metiltransferases/metabolismo , Proteínas Substratos do Receptor de Insulina/genética , MicroRNAs/genética , Neovascularização Patológica/genética , Receptor IGF Tipo 1/genética , Adulto , Idoso , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células , DNA (Citosina-5-)-Metiltransferase 1 , Metilação de DNA , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Proteínas Substratos do Receptor de Insulina/metabolismo , Pessoa de Meia-Idade , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Gradação de Tumores , Fosfatidilinositol 3-Quinases/metabolismo , Regiões Promotoras Genéticas , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor IGF Tipo 1/metabolismo , Transdução de Sinais , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
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.
Assuntos
Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Macaca mulatta/genética , MicroRNAs/genética , Neurônios/metabolismo , Envelhecimento/genética , Animais , Apoptose/genética , Células Cultivadas , Feminino , Humanos , Neurônios/citologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , RatosRESUMO
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.
Assuntos
MicroRNAs/genética , MicroRNAs/fisiologia , Peixe-Zebra/embriologia , Peixe-Zebra/genética , Animais , Northern Blotting , Embrião não Mamífero/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/genética , Marcação In Situ das Extremidades Cortadas , MicroinjeçõesRESUMO
The expression of galanin and galanin receptor-2 in hippocampus and dorsal raphe nucleus of depression model was studied. The chronic stress rat model was adopted as the modal of depression. Open-field test was used to observe the transformation of their behavior and HPLC-EC was employed to analysis the level of blood serum cortisol. The method of in situ hybridization was used for testing the expression of Galanin and galanin receptor-2 in hippocampus and dorsal raphe nucleus and the method of RT-PCR was used to further analysis of the expression. The results showed that the locomotion activity decreased extremely after chronic stress, but the level of serum cortisol increased evidently. The expression of Galanin and its receptor-2 in hippocampus and dorsal raphe nucleus increased obviously. The higher expression for galanin and galanin receptor-2 in some brain area suggested that galanin probably takes part in the modulation of the function of neurons during the stress process.
Assuntos
Encéfalo/metabolismo , Depressão/metabolismo , Transtorno Depressivo/metabolismo , Galanina/metabolismo , Hipocampo/metabolismo , Núcleos da Rafe/metabolismo , Receptor Tipo 2 de Galanina/metabolismo , Animais , Modelos Animais de Doenças , Galanina/genética , Expressão Gênica , Masculino , Ratos , Ratos Sprague-Dawley , Receptor Tipo 2 de Galanina/genética , Estresse FisiológicoRESUMO
Olfactory ensheathing cells (OECs) were isolated from newborn rat olfactory bulb and cultured in vitro. RT-PCR was used to determine the expression of galanin and it's receptors in these cells. MTT analysis was used to detect the effects of galanin and agonist, antagonist of galanin receptors on the proliferation of OECs. Results show that OECs express mRNAs for galanin and GalR2 but not for two another receptors, GalR1 and GalR3. In addition, galanin and two receptor agonists, GAL1-11 and GAL2-11, can significantly inhibit the proliferation of OECs. But the influence can be blocked by M35, nonspecific antagonist of galanin receptors.
