RESUMEN
Metastasis is the leading cause of cancer-related death in almost all types of cancers, including colorectal cancer (CRC). Metastasis is a complex, multistep, dynamic biological event, and epithelial-mesenchymal transition (EMT) is a critical process during the cascade. Ajuba family proteins are LIM domain-containing proteins and are reported to be transcription repressors regulating different kinds of physiological processes. However, the expression and pathological roles of Ajuba family proteins in tumors, especial in tumor metastasis, remain poorly studied. Here, we found that JUB, but not the other Ajuba family proteins, was highly upregulated in clinical specimens and CRC cell lines. Ectopic expression of JUB induced EMT and enhanced motility and invasiveness in CRC, and vice versa. Mechanistic study revealed that JUB induces EMT via Snail and JUB is also required for Snail-induced EMT. The expression of JUB shows an inverse correlation with E-cadherin expression in clinical specimens. Taken together, these findings revealed that the LIM protein JUB serves as a tumor-promoting gene in CRC by promoting EMT, a critical process of metastasis. Thus, the LIM protein JUB may provide a novel target for therapy of metastatic CRC.
Asunto(s)
Neoplasias Colorrectales/patología , Transición Epitelial-Mesenquimal , Proteínas con Dominio LIM/metabolismo , Células CACO-2 , Cadherinas/biosíntesis , Movimiento Celular , Neoplasias Colorrectales/genética , Células HCT116 , Humanos , Proteínas con Dominio LIM/genética , Invasividad Neoplásica , Metástasis de la Neoplasia , Interferencia de ARN , ARN Interferente Pequeño , Transducción de Señal , Factores de Transcripción de la Familia Snail , Esferoides Celulares/patología , Factores de Transcripción/metabolismo , Células Tumorales Cultivadas , Regulación hacia ArribaRESUMEN
BACKGROUND: Colorectal cancer (CRC) is one of the most common cancers worldwide and a leading cause of cancer related death. Although the mortality rate of CRC is decreasing, finding novel targets for its therapy remains urgent. Carboxypeptidase E (CPE), a member of the pro-protein convertases, which are involved in the maturation of protein precursors, has recently been reported as elevated in many types of cancer. However, its role and mechanisms in tumor progression are poorly understood. METHODS: In the present study, we investigated expression of CPE in CRC cell lines and tumor tissues using Western blot and real-time qRT-PCR. Plasmids for overexpression and depletion of CPE were constructed and analyzed by Western blot, MTT and colony formation assays and bromodeoxyuridine incorporation assays. The relative expression of p21, p27, and cyclin D1 were analyzed by Real-time qRT-PCR in the indicated cells. RESULTS: Our study showed that CPE was significantly upregulated in CRC cell lines and tumor tissues. MTT and colony formation assays indicated that overexpression of CPE enhanced cell growth rates. BrdU incorporation and flow-cytometry assays showed that ectopic expression of CPE increased the S-phase fraction cells. Soft agar assay proved enhanced tumorigenicity activity in CPE over-expressing CRC cells. Further studies of the molecular mechanisms of CPE indicated that is promoted cell proliferation and tumorigenicity through downregulation of p21 and p27, and upregulation of cyclin D1. CONCLUSIONS: Taken together, these data suggest that CPE plays an important role in cell cycle regulation and tumorigenicity, and may serve as a potential target for CRC therapeutics.
Asunto(s)
Carboxipeptidasa H/genética , Transformación Celular Neoplásica/genética , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Regulación Neoplásica de la Expresión Génica , Carboxipeptidasa H/metabolismo , Línea Celular Tumoral , Proliferación Celular , Ciclina D1/genética , Ciclina D1/metabolismo , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/genética , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/metabolismo , Expresión Génica , Técnicas de Silenciamiento del Gen , Humanos , Fase S/genética , Regulación hacia ArribaRESUMEN
The laurel family within the Magnoliids has attracted attentions owing to its scents, variable inflorescences, and controversial phylogenetic position. Here, we present a chromosome-level assembly of the Litsea cubeba genome, together with low-coverage genomic and transcriptomic data for many other Lauraceae. Phylogenomic analyses show phylogenetic discordance at the position of Magnoliids, suggesting incomplete lineage sorting during the divergence of monocots, eudicots, and Magnoliids. An ancient whole-genome duplication (WGD) event occurred just before the divergence of Laurales and Magnoliales; subsequently, independent WGDs occurred almost simultaneously in the three Lauralean lineages. The phylogenetic relationships within Lauraceae correspond to the divergence of inflorescences, as evidenced by the phylogeny of FUWA, a conserved gene involved in determining panicle architecture in Lauraceae. Monoterpene synthases responsible for production of specific volatile compounds in Lauraceae are functionally verified. Our work sheds light on the evolution of the Lauraceae, the genetic basis for floral evolution and specific scents.
Asunto(s)
Cromosomas de las Plantas/genética , Evolución Molecular , Especiación Genética , Genoma de Planta , Litsea/genética , Vías Biosintéticas/genética , ADN de Plantas/genética , ADN de Plantas/aislamiento & purificación , Duplicación de Gen , Perfilación de la Expresión Génica , Genómica , Inflorescencia/genética , Litsea/metabolismo , Anotación de Secuencia Molecular , Odorantes , Filogenia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Análisis de Secuencia de ADNRESUMEN
Considering the poor medical conditions in some regions of China, this paper attempts to develop a simple and easy way to extract and process the bone features of blurry medical images and improve the diagnosis accuracy of osteoporosis as much as possible. After reviewing the previous studies on osteoporosis, especially those focusing on texture analysis, a convexity optimization model was proposed based on intra-class dispersion, which combines texture features and shape features. Experimental results show that the proposed model boasts a larger application scope than Lasso, a popular feature selection method that only supports generalized linear models. The research findings ensure the accuracy of osteoporosis diagnosis and enjoy good potentials for clinical application.
Asunto(s)
Interpretación de Imagen Asistida por Computador , Lentes , Microscopía , Osteoporosis/diagnóstico , Osteoporosis/patología , Algoritmos , Animales , Modelos Animales de Enfermedad , Femenino , Interpretación de Imagen Asistida por Computador/métodos , Microscopía/instrumentación , Microscopía/métodos , Distribución Aleatoria , Ratas Sprague-Dawley , Sensibilidad y Especificidad , Tibia/patología , Tomografía Computarizada por Rayos XRESUMEN
Neuroblastoma (NB), ganglioneuroblastoma intermixed (GNBi) and ganglioneuroblastoma nodular (GNBn) are neuroblastic tumors that present with a wide range of symptoms and variable prognoses. We retrospectively reviewed the pretreatment clinical (age, sex and tumor stage) and biological (MYCN amplification; and levels of lactate dehydrogenase, ferritin and neuron-specific enolase) characteristics of 279 patients who were diagnosed with pathologically confirmed NB and GNB from January 2005 to December 2015. The median age at diagnosis increased with grade of differentiation (NB: 28.9 months; GNBn: 38.4 months; GNBi: 47.5 months; p < 0.01). NB patients were more frequently diagnosed with adrenal tumors and had a higher prevalence of abnormal serum ferritin at the time of diagnosis (60.0% vs. 40.0% vs. 12.0%, P<0.001), NSE (96.0% vs. 93.0% vs. 81.0%, P=0.013) when compared with GNBn and GNBi patients. The prevalence rates of disseminated tumors and MYCN amplified tumors were lower in the GNBi group than in the GNBn and NB groups (13.0% vs. 25.0% vs. 44.0%, P=0.002; 0 vs. 14.0% vs. 26.0%, P=0.032, respectively). The overall survival (OS) of patients with GNB was significantly better than that of patients with NB (GNBi: 100%, GNBn: 74.5±11.4%, NB: 50.8±4.5%, respectively; P<0.01). Our study revealed that both NB and GNB have a wide range of presentations, and clinicians should be aware of both typical and atypical symptoms and signs. Children with GNB (especially GNBi) were more likely to present favorable prognostic factors than their NB counterparts, which consequently lead to better outcomes and longer survival for these patients.
Asunto(s)
Ganglioneuroblastoma , Neuroblastoma , Adulto , Femenino , Ganglioneuroblastoma/mortalidad , Ganglioneuroblastoma/patología , Humanos , Masculino , Neuroblastoma/mortalidad , Neuroblastoma/patología , Estudios Retrospectivos , Análisis de SupervivenciaRESUMEN
Hepatocellular carcinoma (HCC) is one of the most common human malignancies and the third leading cause of cancer mortality worldwide. The development and progression of HCC is a complicated process, involving the deregulation of multiple genes that are essential to cell biological processes. Recently, microRNAs (miRNAs) have been suggested to be closely associated with tumorigenesis. Our study showed that miR-184 is upregulated in HCC cell lines and tissues. Overexpression of miR-184 in HCC cells increased cell proliferation, tumorigenicity, and cell cycle progression, whereas inhibition of miR-184 reduced cell proliferation, tumorigenicity, and cell cycle progression. Additionally, we identified SOX7 as a direct target of miR-184. Ectopic expression of miR-184 led to downregulation of the SOX7 protein, resulting in upregulation of c-Myc, Cyclin D1, and phosphorylation of Rb. Our findings suggested that miR-184 represents a potential onco-miR and plays an important role in HCC progression by suppressing SOX7 expression.
Asunto(s)
Carcinoma Hepatocelular/patología , Regulación Neoplásica de la Expresión Génica/genética , Neoplasias Hepáticas/patología , MicroARNs/genética , Factores de Transcripción SOXF/genética , Secuencia de Bases , Carcinogénesis/genética , Ciclo Celular/genética , Línea Celular Tumoral , Proliferación Celular , Humanos , ARN Mensajero/genética , ARN Mensajero/metabolismoRESUMEN
Obesity increases the incidence, progression and mortality of breast cancer among postmenopausal females. This is partly due to excessive estrogen production in the adipose tissue of obese females. Aromatase is a key enzyme in estrogen biosynthesis. In the current study, the tensional forcetriggered inducibility of aromatase expression was observed to vary in ASCs isolated from different diseasefree individuals. In addition, this phenomenon was associated with the activation of the aromatase PII promoter and its DNA methylation load. These findings highlight the impact of tensional forces on estrogen biosynthesis in obese females.