RESUMEN
Subsequently to the publication of the above article, the authors contacted the Editorial Office to explain that they had inadvertently included data from the same original source in the first row of data panels in Fig. 4B on p. 2191 (showing the results of cell migration assay experiments) to represent two differently performed experiments. Specifically, these images (second and third data panels) containing partially overlapping data corresponded to the 'VacantBGC823' in the empty plasmid transfection group and the background 'BGC823 cell' groups, respectively. However, the authors had retained their original data, which they presented to the office for our inspection, and were able to reassemble the data correctly in the figure. The revised version of Fig. 4, showing the replacement data for the 'VacantBGC823' and 'BGC823' Migration panels in Fig. 4B, is shown on the next page. The authors are grateful to the Editor of International Journal of Oncology for allowing them this opportunity to publish a Corrigendum, and all the authors agree with its publication. Furthermore, the authors apologize to the readership for any inconvenience caused. [International Journal of Oncology 48: 21842196, 2016; DOI: 10.3892/ijo.2016.3428].
RESUMEN
Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that certain of the cell Transwell assay data in the article (featured in Figs. 3B and 6B) were strikingly similar to data that appearing in different form in another article by different authors at different research institutions, which had already been published elsewhere at the time of the present article's submission. Owing to the fact that the contentious data in the above article had already appeared in different form in another article prior to its submission to Oncology Reports, the Editor has decided that this paper should be retracted from the Journal. The authors did not reply to indicate whether or not they agreed with the retraction of the paper. The Editor apologizes to the readership for any inconvenience caused. [the original article was published on Oncology Reports 34: 399406, 2015; DOI: 10.3892/or.2015.3986].
RESUMEN
Breast cancer is the leading cause of cancer deaths in females all over the world, mainly resulting from metastasis. Previous studies have revealed that repressor element-1 (RE-1) silencing transcription (REST) acted as a tumor suppressor in breast cancer. However, the mechanism by which REST is regulated remains unknown, and its role in the metastasis in breast cancer cells remains unclear. In the present study, we showed that the expression of REST was lower in breast cancer samples than that of adjacent samples by immunohistochemical analysis, which may be due to hypermethylation of the REST promoter. Low REST levels are significantly associated with malignant progression in breast cancer patients. Additionally, we elucidated the functions of REST on proliferation and invasion in breast cancer cells. Lentivirus transfection was used to overexpress REST in human breast MDA-MB-231 cells. Then the biologic consequences of overexpressing REST in regard to cell proliferation, apoptosis, and invasion were determined. Furthermore, we also determined matrix metalloproteinase-9 (MMP9) as a target of REST. These results demonstrate that downregulation of REST, a tumor suppressor in breast cancer, is associated with hypermethylation. Induced REST expression is capable of attenuating invasion ability of breast cancer cells, which may be a novel strategy for metastatic breast cancer treatment.
Asunto(s)
Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Metaloproteinasa 9 de la Matriz/genética , Proteínas Represoras/genética , Apoptosis/genética , Línea Celular Tumoral , Proliferación Celular/genética , Metilación de ADN/genética , Regulación hacia Abajo/genética , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Células MCF-7 , Invasividad Neoplásica/genética , Fenotipo , Regiones Promotoras Genéticas/genética , Transfección/métodosRESUMEN
Ovarian carcinoma is the most lethal gynecologic tumor worldwide. Despite having developed molecular diagnostic tools and targeted therapies over the past few decades, patient survival is still quite poor. Numerous studies suggest that microRNAs are key regulators of many fundamental biological processes, including neoplasia and tumor progression. miR-222 is one of those miRNAs that has attracted much attention for its multiple roles in human diseases, especially cancer. The potential role of microRNAs in ovarian cancer has attracted much attention in recent years. Some of these microRNAs have been suggested as potential therapeutic targets for EOC patients. In this study, we sought to investigate the biologic functions of miR-222-3p in EOC carcinogenesis. Herein, we examined the expression of miR-222-3p in EOC patients, mouse models and cell lines, and found that higher expression of miR-222-3p was associated with better overall survival in EOC patients, and its level was negatively correlated with tumor growth in vivo. Furthermore, in-vitro experiments indicated that miR-222-3p inhibited EOC cell proliferation and migration, and decreased the phosphorylation of AKT. We identified GNAI2 as a target of miR-222-3p. We also found that GNAI2 promoted EOC cell proliferation, and is an activator of the PI3K/AKT pathway. We describe the characterization of a novel regulatory axis in ovarian cancer cells, miR-222-3p/GNAI2/AKT and its potential application as a therapeutic target for EOC patients.
Asunto(s)
Proliferación Celular , Subunidad alfa de la Proteína de Unión al GTP Gi2/metabolismo , MicroARNs/metabolismo , Neoplasias Glandulares y Epiteliales/enzimología , Neoplasias Ováricas/enzimología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Regiones no Traducidas 3' , Adulto , Anciano , Animales , Sitios de Unión , Carcinoma Epitelial de Ovario , Línea Celular Tumoral , Movimiento Celular , Femenino , Subunidad alfa de la Proteína de Unión al GTP Gi2/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Estimación de Kaplan-Meier , Ratones Desnudos , MicroARNs/genética , Persona de Mediana Edad , Clasificación del Tumor , Invasividad Neoplásica , Neoplasias Glandulares y Epiteliales/genética , Neoplasias Glandulares y Epiteliales/metabolismo , Neoplasias Glandulares y Epiteliales/mortalidad , Neoplasias Ováricas/genética , Neoplasias Ováricas/metabolismo , Neoplasias Ováricas/mortalidad , Fosforilación , Modelos de Riesgos Proporcionales , Interferencia de ARN , Transducción de Señal , Factores de Tiempo , Transfección , Carga Tumoral , Adulto JovenRESUMEN
CXCR1 is a member of the chemokine receptor family, which was reported to play an important role in several cancers. The present study investigated the influence of CXCR1 stable knockdown or overexpression on the malignant behavior of gastric cancer cells in vitro and in vivo and the potential mechanisms. MKN45 and BGC823 cells were stably transfected with plasmid pYr-1.1-CXCR1-shRNA (knockdown) and pIRES2-ZsGreen1-CXCR1 (overexpression), respectively. Malignant behavior was evaluated in vitro for changes in proliferation by MTT and colony forming assays; cell cycle and apoptosis by flow cytometry; and migration and invasion using transwell and wound-healing assays. Proliferation, cell cycle, apoptosis, migration and invasion-related signaling molecule expression were measured by real-time RT-PCR and western blot analysis. CXCR1 knockdown and overexpressing xenografts were monitored for in vivo tumor growth. Stable knockdown of CXCR1 inhibited MKN45 cell proliferation, migration and invasion, but were reversed in BGC823 cells stably overexpressing CXCR1. In addition, MKN45 cells stably transfected with CXCR1 shRNA inhibited AKT and ERK1/2 phosphorylation, protein expression of cyclin D1, EGFR, VEGF, MMP-9, MMP-2 and Bcl-2, and increased protein expression of Bax and E-cadherin (all P<0.05). In vivo CXCR1-shRNA-MKN45 cells transplanted into nude mice formed smaller tumors than non-transfected or scrambled-shRNA cells (both P<0.05). In contrast BGC823 cells overexpressing CXCR1 formed larger tumors in mice than cells carrying an empty expression plasmid or non-transfected cells (both P<0.05). CXCR1 promoted gastric cancer cell proliferation, migration and invasion. The present study provides preclinical data to support CXCR1 as a novel therapeutic target for gastric cancer.
Asunto(s)
Proteínas Proto-Oncogénicas c-akt/metabolismo , Receptores de Interleucina-8A/genética , Receptores de Interleucina-8A/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patología , Animales , Ciclo Celular , Línea Celular Tumoral , Proliferación Celular , Femenino , Regulación Neoplásica de la Expresión Génica , Técnicas de Silenciamiento del Gen , Humanos , Técnicas In Vitro , Sistema de Señalización de MAP Quinasas , Ratones , Trasplante de Neoplasias , Fosforilación , Neoplasias Gástricas/genéticaRESUMEN
Chemokine-mediated activation of G protein-coupled receptors CXCR1/2 promotes tumor growth, invasion, inflammation and metastasis. Repertaxin, a CXCR1/2 small-molecule inhibitor, has been shown to attenuate many of these tumor-associated processes. The present study aimed to investigate the effects of repertaxin alone and in combination with 5-fluorouracil (5-FU) on the malignant behavior of gastric cancer and the potential mechanisms. Gastric cancer MKN45 cells were treated in vitro with repertaxin and 5-FU, either alone or in combination. MTT and colony formation assay were performed to assess proliferation. Cell cycle progression and apoptosis was completed by flow cytometry. Migration and invasion were also assessed by transwell and wound-healing assay. Western blot analysis and quantitative RT-PCR were performed to determine expression of signaling molecules. MKN45 cells were also grown as xenografts in nude mice. Mice were treated with repertaxin and 5-FU, and tumor volume and weight, angiogenesis, proliferation and apoptosis were monitored. Combination of repertaxin and 5-FU inhibited MKN45 cell proliferation and increased apoptosis better than either agent alone. Similarly, enhanced effect of the combination was also observed in migration and invasion assays. The improved effect of repertaxin and 5-FU was also observed in vivo, as xenograft models treated with both compounds exhibited significantly decreased tumor volume and increased apoptosis. In conclusion, repertaxin inhibited malignant behavior of human gastric cancer MKN45 cells in vitro and in vivo and enhances efficacy of 5-fluorouracil. These data provide rationale that targeting CXCR1/2 with small molecule inhibitors may enhance chemotherapeutic efficacy for the treatment of gastric cancer.
Asunto(s)
Receptores de Interleucina-8A/biosíntesis , Receptores de Interleucina-8B/biosíntesis , Neoplasias Gástricas/tratamiento farmacológico , Sulfonamidas/administración & dosificación , Animales , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Cisplatino/administración & dosificación , Resistencia a Antineoplásicos , Fluorouracilo/administración & dosificación , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Ratones , Receptores de Interleucina-8A/antagonistas & inhibidores , Receptores de Interleucina-8B/antagonistas & inhibidores , Transducción de Señal/efectos de los fármacos , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
The complete mitochondrial genome of Boettcherisca peregrine (B. peregrina), an important forensic entomology, was sequenced for the first time. The 14,922 bp circular genome contains 37 genes that were found in a typical Metazoan genome: 13 protein-coding genes, 22 transfer RNA genes and 2 ribosomal RNA genes. It also contains one non-coding A + T-rich region. The arrangement of the genes was the same as that found in the other insect. The overall base composition on heavy strand was as follows: A, 38.86%; G, 15.10%; C, 9.93%; T, 36.11%; and the A + T content 74.97%. The mitochondrial genome of Sarcophaga presented could be valuable for resolving phylogenetic relationships within the order Diptera and especially for the family Sarcophagidae. The molecular data presented may also be used to screen favorable molecular markers for species identifications for forensic entomology purposes.
Asunto(s)
Genoma Mitocondrial/genética , Sarcofágidos/genética , Análisis de Secuencia de ADN , Animales , Entomología , Genética Forense , Genes de ARNr , Anotación de Secuencia Molecular , Datos de Secuencia Molecular , Sistemas de Lectura Abierta/genética , ARN de Transferencia/genéticaRESUMEN
More than 1400 scuttle flies species in worldwide comprise the Megaselia genus, the largest genus in the family Phoridae. The complete mitochondrial genome of Megaselia scalaris, a medically important entomology was sequenced for the first time. The 15,599 bp circular genome contains the 37 genes found in a typical Metazoan genome: 13 protein-coding genes, 22 transfer RNA genes and 2 ribosomal RNA genes. The mitochondrial genome also contains one non-coding A + T-rich region. The arrangement of the genes was identical with other insect. Each of the base composition on heavy strand was as follows A: 38.87%, G: 13.74%, C: 9.46%, T: 37.93% and the A + T content 76.80%. The mitochondrial genome of M. scalaris presented may be valuable for determining phylogenetic relationships within the order Diptera and especially for the family Phoridae. These sequences could also be used to select reliable molecular markers for species identification in forensic entomology.
Asunto(s)
Dípteros/genética , Genoma de los Insectos , Genoma Mitocondrial , Animales , Emparejamiento Base/genética , Secuencia de Bases , ADN Mitocondrial/genética , Genes de Insecto , Tamaño del Genoma , Filogenia , Análisis de Secuencia de ADNRESUMEN
The overall goal of the present study was to find and validate unidentified miRNAs that regulate epithelial-mesenchymal transition (EMT) and proliferation in ovarian cancer. Furthermore, we demonstrate that the high expression of miR-153 in human epithelial ovarian cancer (EOC) is associated with better survival. The mean expression level of miR-153 in ovarian cancer was significantly lower than in the adjacent carcinoma tissue. In the present study, we report that miR-153 are negative regulators of SET7 and ZEB2, miR-153 regulates SET7/ZEB2 expression and promotes SET7/ZEB2 mRNA degradation. Further, confirmed by reporter assays, SET7/ZEB2 are downstream targets of miR-153 directly bound to the 3' untranslated region (3'-UTR). Clone formation and wound-healing assay as well as Transwell assay proved that silencing of SET7 or ZEB2 partially abolished the enhancement of cell proliferation and invasion induced by downregulated miR-153. SET7 and ZEB2 are negatively correlated with miR-153 expression in human ovarian cancer and indicated a worse survival. Considering the role of SET7 and ZEB2 in EOC, it is important to clarify how the expression of SET7 and ZEB2 are regulated. Based on our results miR-153 inhibits proliferation and suppresses EMT and the invasive potential of ovarian cancer cells through downregulation of SET7 and ZEB2, supporting the pursuit of miR-153 as a potential target for ovarian cancer intervention.
Asunto(s)
N-Metiltransferasa de Histona-Lisina/biosíntesis , Proteínas de Homeodominio/biosíntesis , MicroARNs/genética , Neoplasias Ováricas/genética , Proteínas Represoras/biosíntesis , Regiones no Traducidas 3' , Línea Celular Tumoral , Proliferación Celular/genética , Transición Epitelial-Mesenquimal/genética , Femenino , Regulación Neoplásica de la Expresión Génica , N-Metiltransferasa de Histona-Lisina/genética , Proteínas de Homeodominio/genética , Humanos , Invasividad Neoplásica/genética , Neoplasias Ováricas/patología , Proteínas Represoras/genética , Caja Homeótica 2 de Unión a E-Box con Dedos de ZincRESUMEN
MicroRNAs (miRs) play crucial roles in tumorigenesis by directly suppressing the protein expression levels of their target genes. miR-204 has been suggested to act as a tumor suppressor in several types of human cancer. However, the exact role of miR-204 in osteosarcoma (OS) remains undetermined. In the present study, we aimed to investigate the effects of miR-204 on OS cell proliferation, migration and invasion, as well as the underlying molecular mechanisms. We found that the expression of miR-204 was frequently downregulated in four OS cell lines compared to the level in normal human osteoblast cells. Moreover, overexpression of miR-204 significantly inhibited the proliferation, migration and invasion of OS cells. Based on bioinformatics prediction and a luciferase reporter assay, we identified Sirtuin 1 (Sirt1) as a direct target gene of miR-204 in OS Saso-2 cells. Moreover, the protein expression of Sirt1 was negatively mediated by miR-204 in the OS cells. siRNA-mediated knockdown of Sirt1 also inhibited the proliferation, migration and invasion of the OS cells. Moreover, overexpression of Sirt1 reversed the inhibitory effect of miR-204 overexpression on the proliferation, migration and invasion of the OS cells. In addition, after miR-204 overexpression or Sirt1 knockdown in OS cells, the expression of E-cadherin was increased, while the N-cadherin protein level was reduced. Based on these findings, we suggest that miR-204 inhibits the proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) of OS cells by directly targeting Sirt1.
Asunto(s)
Neoplasias Óseas/patología , Transición Epitelial-Mesenquimal , MicroARNs/metabolismo , Osteosarcoma/patología , Sirtuina 1/genética , Regiones no Traducidas 3' , Neoplasias Óseas/genética , Neoplasias Óseas/metabolismo , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Regulación hacia Abajo , Regulación Neoplásica de la Expresión Génica , Humanos , MicroARNs/genética , Invasividad Neoplásica , Osteosarcoma/genética , Osteosarcoma/metabolismo , Sirtuina 1/metabolismoRESUMEN
MicroRNAs (miRNAs) can serve as biomarkers in human cancer. To determine the clinical value of urinary miRNAs for ovarian serous adenocarcinoma, we collected urine samples from 39 ovarian serous adenocarcinoma patients, 26 patients with benign gynecological disease and 30 healthy controls. The miRNA microarray data showed that only miR-30a-5p was upregulated and 37 miRNAs were downregulated in the urine samples of ovarian serous adenocarcinoma patients, when compared to healthy controls, which was confirmed after conducting quantitative PCR. The upregulation of urinary miR-30a-5p was closely associated with early stage of ovarian serous adenocarcinoma as well as lymphatic metastasis. Receiver operator characteristic (ROC) analysis demonstrated the potential use of urinary miR-30a-5p as a diagnostic marker for ovarian serous adenocarcinoma. Furthermore, a lower urine level of miR-30a-5p was found in 20 gastric cancer and 20 colon carcinoma patients when compared to ovarian serous adenocarcinoma, suggesting that the upregulation of urinary miR-30a-5p may be specific for ovarian serous adenocarcinoma. miR-30a-5p was also upregulated in ovarian serous adenocarcinoma tissues and cell lines, while urinary miR-30a-5p from ovarian cancer patients was notably reduced following the surgical removal of ovarian serous adenocarcinoma, suggesting that urinary miR-30a-5p was derived from the ovarian serous adenocarcinoma tissue. Notably, miR-30a-5p was concentrated with exosomes from the ovarian cancer cell supernatant or urine from ovarian serous adenocarcinoma patients, supporting a pathway for excretion into the urine. The results also showed that the knockdown of miR-30a-5p significantly inhibited the proliferation and migration of ovarian cancer cells. In summary, to the best of our knowledge, the present study provided the first evidence of increased miR-30a-5p in the urine of ovarian serous adeno-carcinoma patients, while the inhibition of miR-30a-5p suppressed the malignant phenotypes of ovarian cancer in vitro. Therefore, miR-30a-5p serves as a promising diagnostic and therapeutic target for ovarian serous adenocarcinoma.
Asunto(s)
Biomarcadores de Tumor/biosíntesis , Cistadenocarcinoma Seroso/genética , MicroARNs/biosíntesis , Neoplasias Ováricas/genética , Anciano , Biomarcadores de Tumor/orina , Línea Celular Tumoral , Cistadenocarcinoma Seroso/patología , Cistadenocarcinoma Seroso/orina , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Metástasis Linfática , MicroARNs/orina , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Ováricas/patología , Neoplasias Ováricas/orinaRESUMEN
BACKGROUND: Serous epithelial ovarian cancer is the most common variety of ovarian cancer and is currently diagnosed using serum CA-125 levels. HMGA1 a small 10.6-12 kDa protein, has been implicated as a potentially important tumor biomarker and may enter the urinary trace, thus potentially able to serve as a disease biomarker. OBJECTIVE: To determine if urine HMGA1 can be detected and potentially serve as a clinical diagnostic biomarkers. METHOD: Urine was collected from 20 healthy normal control patients, 20 patients with benign gynecological disease and 55 epithelial ovarian specimens of which 20 exhibited G1/2 ovarian cancer and 35 G3 ovarian cancers. Serum was also collected from 20 healthy normal control patients and 55 serous epithelial ovarian cancers patients. HMGA1 levels were examined via enzyme-linked immunosorbent assay (ELISA) and were reported independently and normalized to urine creatinine levels. Serum CA-125 levels were examined via enzyme assay and the data was analyzed via box and ROC analysis. RESULTS: Urine HMGA1 was significantly elevated in serous epithelial ovarian cancer specimen relative to healthy control specimens with G3 specimens exhibiting higher levels than G1-G2 specimens. ROC analysis revealed a high degree of sensitivity and specificity for urine HMGA1 detection in ovarian cancer, with a higher AUC value noted for urine HMGA1 than serum CA-125. Furthermore, urine HMGA1 and serum CA-125 combined AUC indicated that urine HMGA1 is an excellent diagnostic biomarker for serous epithelial ovarian cancer. CONCLUSION: Our data indicates that measuring urine HMGA1 may serve as a useful diagnostic tool.
Asunto(s)
Biomarcadores de Tumor/orina , Proteína HMGA1a/orina , Neoplasias Glandulares y Epiteliales/orina , Neoplasias Ováricas/orina , Adulto , Anciano , Antígeno Ca-125/sangre , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Persona de Mediana Edad , Neoplasias Glandulares y Epiteliales/diagnóstico , Neoplasias Ováricas/diagnóstico , Adulto JovenRESUMEN
Extranodal natural killer (NK)/T-cell lymphoma is a very aggressive malignant neoplasia with a poor prognosis. Herein we reported a case of NK/T cell lymphoma involving mediastinum. It was a 28-year-old Chinese male patient. The tumor cells were medium-sized, had irregularly folded nuclei, and inconspicuous or small nucleoli with coagulative necrosis. The tumor cells were positive for CD3ε, TIA-1, but negative for CD56. In situ hybridization revealed that tumor cells also expressed Epstein-Barr virus encoded RNA. To our knowledge, this is the first case of NK/T cell lymphoma involving mediastinum.
Asunto(s)
Epidídimo/patología , Neoplasias de los Genitales Masculinos/patología , Linfoma Extranodal de Células NK-T/patología , Neoplasias del Mediastino/patología , Adulto , Biomarcadores de Tumor/análisis , Biopsia , Epidídimo/inmunología , Epidídimo/virología , Resultado Fatal , Neoplasias de los Genitales Masculinos/inmunología , Neoplasias de los Genitales Masculinos/virología , Herpesvirus Humano 4/genética , Humanos , Inmunohistoquímica , Hibridación in Situ , Linfoma Extranodal de Células NK-T/inmunología , Linfoma Extranodal de Células NK-T/virología , Masculino , Neoplasias del Mediastino/inmunología , Neoplasias del Mediastino/virología , ARN Viral/genética , Factores de Tiempo , Tomografía Computarizada por Rayos XRESUMEN
Epidermal growth factor-like domain-containing protein 7 (EGFL7) is upregulated in human epithelial tumors and so is a potential biomarker for malignancy. Indeed, previous studies have shown that high EGFL7 expression promotes infiltration and metastasis of gastric carcinoma. The epithelial-mesenchymal transition (EMT) initiates the metastatic cascade and endows cancer cells with invasive and migratory capacity; however, it is not known if EGFL7 promotes metastasis by triggering EMT. We found that EGFL7 was overexpressed in multiple human gastric cancer (GC) cell lines and that overexpression promoted cell invasion and migration as revealed by scratch wound and transwell migration assays. Conversely, shRNA-mediated EGFL7 knockdown reduced invasion and migration. Furthermore, EGFL7-overexpressing cells grew into larger tumors and were more likely to metastasize to the liver compared to underexpressing CG cells following subcutaneous injection in mice. EGFL7 overexpression protected GC cell lines against anoikis, providing a plausible mechanism for this enhanced metastatic capacity. In excised human gastric tumors, expression of EGFL7 was positively correlated with expression levels of the mesenchymal marker vimentin and the EMT-associated transcription repressor Snail, and negatively correlated with expression of the epithelial cell marker E-cadherin. In GC cell lines, EGFL7 knockdown reversed morphological signs of EMT and decreased both vimentin and Snail expression. In addition, EGFL7 overexpression promoted EGF receptor (EGFR) and protein kinase B (AKT) phospho-activation, effects markedly suppressed by the EGFR tyrosine kinase inhibitor AG1478. Moreover, AG1478 also reduced the elevated invasive and migratory capacity of GC cell lines overexpressing EGFL7. Collectively, these results strongly suggest that EGFL7 promotes metastasis by activating EMT through an EGFR-AKT-Snail signaling pathway. Disruption of EGFL7-EGFR-AKT-Snail signaling may a promising therapeutic strategy for gastric cancer.
Asunto(s)
Adenocarcinoma/genética , Factores de Crecimiento Endotelial/genética , Receptores ErbB/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias Hepáticas/genética , Proteínas Proto-Oncogénicas c-akt/genética , Neoplasias Gástricas/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/secundario , Adulto , Anciano , Anciano de 80 o más Años , Animales , Proteínas de Unión al Calcio , Línea Celular Tumoral , Movimiento Celular , Familia de Proteínas EGF , Factores de Crecimiento Endotelial/antagonistas & inhibidores , Factores de Crecimiento Endotelial/metabolismo , Transición Epitelial-Mesenquimal/efectos de los fármacos , Receptores ErbB/antagonistas & inhibidores , Receptores ErbB/metabolismo , Femenino , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/secundario , Masculino , Ratones , Ratones Desnudos , Persona de Mediana Edad , Invasividad Neoplásica , Trasplante de Neoplasias , Proteínas Proto-Oncogénicas c-akt/metabolismo , Quinazolinas/farmacología , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo , Transducción de Señal , Factores de Transcripción de la Familia Snail , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patología , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Tirfostinos/farmacología , Vimentina/genética , Vimentina/metabolismoRESUMEN
OBJECTIVE: To analyze the expression of vascular endothelial growth factor (VEGF), miR-205, Ezrinand Lamin A/C in ovarian cancer tissues. METHODS: The expression of VEGF in the serum of epithelial ovarian cancer and that of healthy volunteers were detected by enzyme-linked immunosorbent assay; the expressions of vascular endothelial growth factor receptor 1 (VEGFR-1), VEGFR-2, Ezrin and Lamin A/C were detected by immunohistochemistry and the micro-vessel density (MVD) of CD31 was detected by immunohistochemistry in epithelial ovarian cancer, benign ovarian and normal ovarian specimens; and the expression of miR-205, Ezrin and Lamin A/C were detected by real-time PCR in epithelial ovarian cancer, benign ovarian and normal ovarian specimens. RESULTS: The expression of VEGF in the serum of epithelial ovarian cancer patients (116.10± 11.94) was significantly higher than that of healthy volunteers (40.04±4.97, P<0.05). The positive expression rates of VEGFR-1 and VEGFR-2 in the epithelial ovarian cancer specimens were 75.9% and 91.4% respectively, which were significantly higher than that in the benign ovarian and the normal ovarian specimens (P<0.05). No differences were observed in the positive expression rates of VEGFR-1 and VEGFR-2 between the benign ovarian and the normal ovarian specimens (P>0.05). The average length of MVD in the epithelial ovarian cancer specimens (7.56±0.51), was significantly higher than that in the normal ovarian specimens (1.22±0.56, P<0.05) and in the benign ovarian specimens (0.7±0.39, P<0.05). No differences were observed in the average length of MVD between the benign ovarian and the normal ovarian specimens (P>0.05). The relative expression level of miR-205 was 0.106±0.035 in the epithelial ovarian cancer specimens, which was significantly higher than that in the normal ovarian specimens (0.0007±0.0005, P<0.05); the relative expression level of miR-205 in the benign ovarian specimens was (0.0002±0.0002), higher than that in the normal ovarian specimens, but with no significance (P>0.05). The positive expression rates of Ezrin and Lamin A/C in the epithelial ovarian cancer specimens were 51.7% and 60.3%, respectively, which were significantly lower than those in the benign ovarian and the normal ovarian specimens (P<0.05). No differences were observed in the positive expression rates of Ezrin and Lamin A/C between the benign ovarian and the normal ovarian specimens (P>0.05). The relative expression levels of Ezrin and Lamin A/C mRNA in the epithelial ovarian cancer specimens were (0.026±0.003) and (0.060±0.007), respectively, which were significantly lower than those in the normal ovarian specimens (P<0.05). There was no statistical significance between the relative expression level of Ezrin and Lamin A/C mRNA in the epithelial ovarian cancer specimens and that in the benign ovarian specimens (0.029± 0.011, 0.089 ± 0.019; P>0.05) . CONCLUSION: VEGF is significantly expressed in the serum of epithelial ovarian cancer patients; and miR-205 is up-regulated in the epithelial ovarian cancer specimens. Ezrin and Lamin A/C are down-regulated in the epithelial ovarian cancer samples. VEGF, miR-205 and target protein may be associated with the invasion and metastasis of epithelial ovarian cancer.
Asunto(s)
Proteínas del Citoesqueleto/metabolismo , Lamina Tipo A/metabolismo , MicroARNs/metabolismo , Neoplasias Glandulares y Epiteliales/metabolismo , Neoplasias Ováricas/metabolismo , Factor A de Crecimiento Endotelial Vascular/sangre , Carcinoma Epitelial de Ovario , Proteínas del Citoesqueleto/genética , Regulación hacia Abajo , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Inmunohistoquímica , Lamina Tipo A/genética , MicroARNs/genética , Neoplasias Glandulares y Epiteliales/genética , Neoplasias Ováricas/genética , ARN Mensajero , Reacción en Cadena en Tiempo Real de la Polimerasa , Receptor 1 de Factores de Crecimiento Endotelial Vascular/metabolismo , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismoAsunto(s)
Perfilación de la Expresión Génica/normas , Genes de Insecto/genética , Moscas Domésticas/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/normas , Actinas/genética , Animales , Perfilación de la Expresión Génica/métodos , Gliceraldehído-3-Fosfato Deshidrogenasas/genética , Factor 1 de Elongación Peptídica/genética , ARN Ribosómico 18S/genética , Estándares de Referencia , Reproducibilidad de los Resultados , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Proteínas Ribosómicas/genéticaRESUMEN
OBJECTIVE: To investigate the changes of cyclooxygenase-2 (COX-2) expression in the spinal cord dorsal horn after intrathecal a specific p38MAPK inhibitor-SB203580 on neuropathic pain in rats induced by chronic constrictive injury (CCI) to the sciatic nerve. METHODS: Twenty-four male SD rats after intrathecal catheter placement were randomly divided into 4 groups: a sham group with sham surgery, the neuropathic pain model of a NS group, a DMSO group and an SB group were established by CCI to sciatic nerve. NS or DMSO or SB203580 was injected IT NS or 2%DMSO or SB203580 twice a day for 5 consecutive days starting at 6th day when the model of chronic constrictive injury was established. Mechanical stimuli were measured before the surgery and on 1st, 3rd, 5th, 7th, 9th, and 11th day after the surgery. Then all rats were sacrificed and the lumbar segment of spinal cord was removed to determine the COX-2 expression in the dorsal horn by immunocytochemistry. RESULTS: Day 1 to 11 after the surgery, the threshold to mechanical on the surgery side was significantly lower in the NS group and the DMSO group than in the sham group. Day 7 to 11 after the sugery, the threshold to mechanical on the surgery side was significantly lower in the SB group than in the NS group and the DMSO group. The expression of spinal COX-2 was higher in the NS group and the DMSO group than in the sham group, but lower in the SB group than in NS group and the DMSO group. CONCLUSION: Intrathecal administration of SB203580 has significant analgesic effect in the CCI rat model. Expression of COX-2 is significantly reduced when p38MAPK is inhibited by intrathecal SB203580, and p38MAPK stimulation is essential for COX-2 expression.
Asunto(s)
Ciclooxigenasa 2/metabolismo , Imidazoles/administración & dosificación , Neuralgia/enzimología , Piridinas/administración & dosificación , Asta Dorsal de la Médula Espinal/enzimología , Proteínas Quinasas p38 Activadas por Mitógenos/antagonistas & inhibidores , Animales , Ciclooxigenasa 2/genética , Imidazoles/farmacología , Inyecciones Espinales , Masculino , Neuralgia/fisiopatología , Piridinas/farmacología , Ratas , Ratas Sprague-Dawley , Médula Espinal/enzimologíaRESUMEN
In this study, the expression of eight candidate reference genes, B2M, ACTB, GAPDH, HMBS, HPRT1, TBP, UBC, and YWHAZ, was examined to identify optimal reference genes by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis in two human hepatoma cell lines, BEL-7402 and SMMC-7721, treated with tumor necrosis factor-α (TNF-α) for different time periods. The expression stability of these genes was analyzed by three independent algorithms: geNorm, NormFinder, and BestKeeper. Results showed that TBP was the most stably expressed gene in BEL-7402 and SMMC-7721 cell lines under current experimental conditions, and that the optimal set of reference genes required for accurate normalization was TBP and HMBS, based on the pairwise variation value determined with geNorm. UBC and ACTB were ranked as the least stable genes by same algorithms. Our findings provide evidence that using TBP alone or in combination with HMBS as endogenous controls could be a reliable method for normalizing qRT-PCR data in human hepatoma cell lines treated with TNF-α.
Asunto(s)
Perfilación de la Expresión Génica/normas , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/normas , Factor de Necrosis Tumoral alfa/farmacología , Proteínas 14-3-3/genética , Actinas/genética , Algoritmos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Perfilación de la Expresión Génica/métodos , Gliceraldehído-3-Fosfato Deshidrogenasas/genética , Humanos , Hidroximetilbilano Sintasa/genética , Hipoxantina Fosforribosiltransferasa/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Estándares de Referencia , Reproducibilidad de los Resultados , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Proteína de Unión a TATA-Box/genética , Ubiquitina/genética , Microglobulina beta-2/genéticaRESUMEN
BACKGROUND: Autophagy is a highly conserved mechanism for degradation and recycling of long-lived proteins and damaged organelle to maintain cell homeostasis. Deregulation of autophagy has been associated with tumorigenesis. Beclin 1 is an essential autophagy protein and its upregulation has been observed in most colorectal cancer tissues. However, there is a small population of colorectal cancers with downregulation of Beclin 1. AIM: The purpose of this study was to investigate the role autophagy plays in colorectal cancers with downregulation of Beclin 1. METHODS: LC3 protein, an autophagosome marker, was assessed by ICH and WB in colorectal cancers tissues. An anti-tumor effect of Beclin 1 was examined by introducing exogenous Beclin 1 in vitro. Colony formation assay, growth curves and mouse xenograft were analysed. RESULTS: Our results showed that LC3 was suppressed in the colorectal cancers (9.86 %) with downregulation of Beclin 1. Moreover, overexpression of Beclin 1 inhibited colorectal cancer cell growth and enhanced the rapamycin-induced antitumor effect in vitro. CONCLUSION: Downregulation of Beclin 1 and autophagy inhibition play an important role in a part of colorectal cancers. Activating autophagy or overexpression of Beclin 1 may be an effective treatment for some colorectal cancers. Detection of expression profile of Beclin 1 in colorectal cancers could be a strategy for new diagnostic and therapeutic methods.