RESUMO
MicroRNA-154 (miR-154) is dysregulated in some human malignancies and is correlated with tumor progression. However, its expression and function in non-small cell lung cancer (NSCLC) remain unclear. Therefore, we explored the effects of miR-154 on NSCLC tumorigenesis and development. Using quantitative reverse transcription-polymerase chain reaction, we detected miR-154 expression in NSCLC cell lines and primary tumor tissues. The association between miR-154 expression and clinicopathological factors was investigated, and the effects of miR-154 on the biological behavior of NSCLC cells were examined. Ultimately, the potential regulatory effect of miR-154 on high-mobility group A2 protein (HMGA2) expression was confirmed. miR-154 was significantly downregulated in NSCLC cell lines and clinical specimens. Reduced miR-154 expression was significantly associated with lymph node metastasis, advanced TNM stage, and shorter overall survival. Multivariate regression analysis confirmed that downregulation of miR-154 was an independent unfavorable prognostic factor for patients with NSCLC. Overexpression of miR-154 inhibited NSCLC cell proliferation, invasion, and migration, and promoted cell apoptosis in vitro. Furthermore, a luciferase reporter assay identified HMGA2 as a direct target of miR-154. Our findings indicate that miR-154 may act as a tumor suppressor in NSCLC and would serve as a novel therapeutic agent for miR-based therapy.
RESUMO
Lipase-producing bacteria are naturally-occurring, industrially-relevant microorganisms that produce lipases, which can be used to synthesize biodiesel from waste oils. The efficiency of lipase expression varies between various microbial strains. Therefore, strains that can produce lipases with high efficiency must be screened, and the conditions of lipase metabolism and optimization of the production process in a given environment must be thoroughly studied. A high efficiency lipase-producing strain was isolated from the sediments of Jinsha River, identified by 16S rRNA sequence analysis as Serratia marcescens, and designated as HS-L5. A schematic diagram of the genome sequence was constructed by high-throughput genome sequencing. A series of genes related to lipid degradation were identified by functional gene annotation through sequence homology analysis. A genome-scale metabolic model of HS-ML5 was constructed using systems biology techniques. The model consisted of 1722 genes and 1567 metabolic reactions. The topological graph of the genome-scale metabolic model was compared to that of conventional metabolic pathways using a visualization software and KEGG database. The basic components and boundaries of the tributyrin degradation subnetwork were determined, and its flux balance analyzed using Matlab and COBRA Toolbox to simulate the effects of different conditions on the catalytic efficiency of lipases produced by HS-ML5. We proved that the catalytic activity of microbial lipases was closely related to the carbon metabolic pathway. As production and catalytic efficiency of lipases varied greatly with the environment, the catalytic efficiency and environmental adaptability of microbial lipases can be improved by proper control of the production conditions.
Assuntos
Proteínas de Bactérias/metabolismo , Genoma Bacteriano/genética , Lipase/metabolismo , Biologia de Sistemas/métodosRESUMO
Osteogenesis imperfecta (OI) is a genetically heterogeneous group of disorders, characterized by abnormal bone fragility, blue sclera, deafness, joint laxity, and soft-tissue dysplasia. The purpose of this study was to elucidate the genetic or molecular basis for OI type IA in a Chinese family. We evaluated the members of a family, in which six individuals are affected with increased bone fragility and blue sclera. Results of exome sequencing revealed a novel 1-bp deletion (c.2329delG, p.A777fs) in exon 33 of the COL1A1 gene in two affected individuals, but not in a control family member without OI. The variation co-segregated with the disease in all the OI patients but not in the unaffected family members. The mutation caused a frameshift alteration after codon 777, leading to premature termination of the COL1A1 protein. Thus, our findings identified a novel frameshift deletion c.2329delG (p.A777fs) in the COL1A1 gene, which is associated with OI type IA in a Chinese family.
Assuntos
Povo Asiático/genética , Colágeno Tipo I/genética , Dentinogênese Imperfeita/genética , Mutação da Fase de Leitura/genética , Osteogênese Imperfeita/genética , Deleção de Sequência/genética , Cadeia alfa 1 do Colágeno Tipo I , Éxons/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , LinhagemRESUMO
Aniridia is an autosomal dominant disorder characterized by the complete or partial loss of the iris and is almost associated with mutations in the paired box gene 6 (PAX6). We examined three generations of a Chinese family with congenital aniridia and observed genetic defects. Exons of PAX6 from 12 family members were amplified by polymerase chain reaction, sequenced, and compared with reference sequences in NCBI reference sequence database (http://www.ncbi.nlm.nih.gov/nuccore/NG_008679.1?from=5001&to=38170&report=genbank). A rare mutation c.2T>A (M1K) in exon 4 of PAX6 was identified in all affected family members but not in unaffected family members. Our results suggest that the c.2T>A (M1K) mutation may be responsible for the pathogenesis of congenital aniridia in this family. To our knowledge, this is the first report of the M1K mutation in PAX6 in a Chinese family with this disease and the second report worldwide.
Assuntos
Aniridia/diagnóstico , Aniridia/genética , Proteínas do Olho/genética , Proteínas de Homeodomínio/genética , Mutação , Fatores de Transcrição Box Pareados/genética , Proteínas Repressoras/genética , Adolescente , Adulto , Sequência de Aminoácidos , Povo Asiático/genética , China , Topografia da Córnea , Análise Mutacional de DNA , Éxons , Proteínas do Olho/química , Família , Feminino , Proteínas de Homeodomínio/química , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Fator de Transcrição PAX6 , Fatores de Transcrição Box Pareados/química , Linhagem , Proteínas Repressoras/química , Alinhamento de Sequência , Adulto JovemRESUMO
The aim of this study was to understand the effect of autologous bone powder graft repair of partial mandibular defects of rabbits by the quantitative detection of bone formation. New Zealand rabbits (N = 18) were selected as the test objects, and subjected to bilateral partial mandibular defect induction. One side of the mandibular defect acted as the test group, upon which the autologous bone powder backfilling graft was performed; the other side was put aside and acted as the negative control group. All used an autogenous control. At the twelfth postoperative week, the animals were sacrificed, and semi-automatic image analysis was used to conduct bone histomorphometric detection. Immediately subsequent, quantitative detection of bone formation was performed in the test group. Fluorescent perimeter percent, mineralization apposition rate, and bone formation rate were selected as the dynamic indicators; and trabecular area percent, trabecular thickness, trabecular number, and trabecular separation degree were selected as the static indicators for single factorial variance testing. It was found that the values of P are less than 0.05 between the test group and the control group, indicating that the effect of autologous bone powder graft repair on partial mandibular defects in rabbits was positive.