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Background: Dysregulation of fatty acid metabolism (FAM) represents a significant metabolic alteration in tumorigenesis. However, the role of FAM-related genes (FAMRGs) in early-stage lung squamous cell carcinoma (LUSC) remains incompletely understood. Methods: A series of bioinformatic analyses and machine learning strategies were performed to construct a FAMRGs-based signature to predict prognosis and guide personalized treatment for early-stage LUSC patients. FAMRGs were screened through the Kyoto Encyclopedia of Genes and Genomes (KEGG) database and the Molecular Signature Database (MSigDB). Prognosis FAMRGs were identified using univariate Cox regression, and unsupervised clustering analysis facilitated the division of the cohort into different clusters. The least absolute shrinkage and selection operator (LASSO)-Cox regression and multivariate regression analysis were employed to develop a FAMRGs-based signature for predicting overall survival (OS). A nomogram was subsequently constructed to facilitate risk assessment for individual patients. Comprehensive analyses of metabolic pathways, immune infiltration, immunomodulators, and potentially applicable drugs were conducted across different FAMRGs-related risk groups. Results: The FAMRGs-based signature, comprising nine genes (ACOT11, APOH, BMX, CYP2R1, DPEP3, FABP6, FADS2, GLYATL2, and THRSP), demonstrated robust predictive capabilities for prognosis in The Cancer Genome Atlas (TCGA)-LUSC dataset and validated across six independent Gene Expression Omnibus (GEO)-LUSC datasets. Notably, the FAMRGs-base signature exhibited superior prognostic capacity and accurate survival prediction compared to conventional clinicopathological features. Furthermore, the signature was closely associated with immune cell infiltration, human leukocyte antigen (HLA) genes, and immune checkpoint genes expression. Additionally, the signature demonstrated potential sensitivity to chemo-/target-therapy. Conclusions: The FAMRGs-based signature demonstrated superior sensitivity in predicting the prognosis of early-stage LUSC. Detecting FAMRGs may provide predictive targets for the development of clinical treatment strategies.
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BACKGROUND: Cell-free DNA (cfDNA) has shown promise in detecting various cancers, but the diagnostic performance of cfDNA end motifs for multiple cancer types requires verification. This study aimed to assess the utility of cfDNA end motifs for multi-cancer detection. METHODS: This study included 206 participants: 106 individuals with cancer, representing 20 cancer types, and 100 healthy individuals. The participants were divided into training and testing cohorts. All plasma cfDNA samples were profiled by whole-genome sequencing. A random forest model was constructed using cfDNA 4 bp-end-motif profiles to predict cancer in the training cohort, and its performance was evaluated in the testing cohort. Additionally, a separate random forest model was developed to predict immunotherapy responses. RESULTS: In the training cohort, the model based on 4 bp-end-motif profiles achieved an AUC of 0.962 (95% CI 0.936-0.987). The AUC in the testing cohort was 0.983 (95% CI 0.960-1.000). The model also maintained excellent predictive ability in different tumor sub-cohorts, including lung cancer (AUC 0.918, 95% CI 0.862-0.974), gastrointestinal cancer (AUC 0.966, 95% CI 0.938-0.993), and other cancer cohort (AUC 0.859, 95% CI 0.776-0.942). Moreover, the model utilizing 4 bp-end-motif profiles exhibited sensitivity in identifying responders to immunotherapy (AUC 0.784, 95% CI 0.609-0.960). CONCLUSION: The model based on 4 bp-end-motif profiles demonstrates superior sensitivity in multi-cancer detection. Detection of 4 bp-end-motif profiles may serve as potential predictive biomarkers for cancer immunotherapy.
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Ácidos Nucleicos Libres de Células , Neoplasias Pulmonares , Humanos , Biomarcadores , Pronóstico , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Ácidos Nucleicos Libres de Células/genética , InmunoterapiaRESUMEN
BACKGROUND: Lung adenocarcinoma (LUAD) is a common subtype of lung cancer with high recurrence rate and fatality. Circ_0001361 has been recognized as key regulators in various malignancies, but its roles in LUAD remain ambiguous. METHODS: Circ_0001361, miR-525-5p, and VMA21 levels were assessed by RT-qPCR. The growth and metastasis of LUAD cells were detected by MTT, colony formation, wound scratch, and transwell assays, respectively. The interaction between circ_0001361/VMA21 and miR-525-5p was detected by dual luciferase, RNA immunoprecipitation, and RNA pull-down assays. VMA21 protein level was detected by Western blotting. Nude mouse xenograft model was established to determine the role of circ_0001361 in tumor growth in vivo. RESULTS: Circ_0001361 was up-regulated, while miR-525-5p was down-regulated in LUAD tissues and cells. Functional experiments demonstrated that circ_0001361 drove LUAD cell growth and metastasis. Mechanistically, circ_0001361 functioned as a sponge of miR-525-5p to up-regulate downstream target VMA21 level. MiR-525-5p/VMA21 axis was involved in circ_0001361-mediated malignant phenotypes of LUAD cells. Finally, inhibition of circ_0001361 restrained in vivo xenograft tumor growth via regulating miR-525-5p/VMA21 axis. CONCLUSION: Our findings elucidate that circ_0001361 facilitates the tumorigenesis and development of LUAD through miR-525-5p/VMA21 axis, providing evidence for circ_0001361 as a potential prognosis biomarker and therapeutic target for clinical treatment of LUAD.
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Adenocarcinoma del Pulmón , Neoplasias Pulmonares , MicroARNs/metabolismo , ATPasas de Translocación de Protón Vacuolares/metabolismo , Adenocarcinoma del Pulmón/genética , Animales , Humanos , Neoplasias Pulmonares/genética , Ratones , MicroARNs/genética , Recurrencia Local de Neoplasia , ARN Circular , ATPasas de Translocación de Protón Vacuolares/genéticaRESUMEN
Circular RNAs (circRNAs) are novel single-stranded noncoding RNAs that can decoy other RNAs to inhibit their functions. Kaposi's sarcoma (KS), caused by oncogenic Kaposi's sarcoma-associated herpesvirus (KSHV), is a highly angiogenic and invasive vascular tumor of endothelial origin commonly found in AIDS patients. We have recently shown that KSHV-encoded viral interferon regulatory factor 1 (vIRF1) induces cell invasion, angiogenesis and cellular transformation; however, the role of circRNAs is largely unknown in the context of KSHV vIRF1. Herein, transcriptome analysis identified 22 differentially expressed cellular circRNAs regulated by vIRF1 in an endothelial cell line. Among them, circARFGEF1 was the highest upregulated circRNA. Mechanistically, vIRF1 induced circARFGEF1 transcription by binding to transcription factor lymphoid enhancer binding factor 1 (Lef1). Importantly, upregulation of circARFGEF1 was required for vIRF1-induced cell motility, proliferation and in vivo angiogenesis. circARFGEF1 functioned as a competing endogenous RNAs (ceRNAs) by binding to and inducing degradation of miR-125a-3p. Mass spectrometry analysis demonstrated that glutaredoxin 3 (GLRX3) was a direct target of miR-125a-3p. Knockdown of GLRX3 impaired cell motility, proliferation and angiogenesis induced by vIRF1. Taken together, vIRF1 transcriptionally activates circARFGEF1, potentially by binding to Lef1, to promote cell oncogenic phenotypes via inhibiting miR-125a-3p and inducing GLRX3. These findings define a novel mechanism responsible for vIRF1-induced oncogenesis and establish the scientific basis for targeting these molecules for treating KSHV-associated cancers.
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Proteínas Portadoras/metabolismo , Factores de Intercambio de Guanina Nucleótido/genética , Herpesvirus Humano 8/fisiología , Factores Reguladores del Interferón/metabolismo , Neovascularización Patológica/patología , ARN Circular/genética , Sarcoma de Kaposi/patología , Proteínas Virales/metabolismo , Proteínas Portadoras/genética , Movimiento Celular , Células Endoteliales de la Vena Umbilical Humana , Humanos , Factores Reguladores del Interferón/genética , MicroARNs/genética , Neovascularización Patológica/genética , Neovascularización Patológica/metabolismo , Neovascularización Patológica/virología , Sarcoma de Kaposi/genética , Sarcoma de Kaposi/metabolismo , Sarcoma de Kaposi/virología , Proteínas Virales/genéticaRESUMEN
Increasing studies on malignant tumors have proposed a new competing endogenous RNA (ceRNA) regulatory mechanism that mRNA, miRNA and lncRNA interact with each other. However, the mRNA-miRNA-lncRNA associated ceRNA network in gastric cancer remains unknown. We used online bioinformatic softwares to predict the hub genes and their upstream miRNAs and lncRNAs in gastric cancer, and then performed survival analyses. After collecting gastric cancer tissue samples and performing PCR experiments, the correlations among predicted mRNA, miRNA and lncRNA were further verified. A total of 101 up-regulated significant differentially expressed genes (DEGs) and 219 down-regulated significant DEGs in gastric cancer were confirmed. Functional enrichment analyses of these significant DEGs indicated that they were potentially enriched in some pathways involved in tumor malignant biological processes or metabolism. Then, we identified 20 hub genes in the PPI networks. Combined with expression and survival analyses, 8 up-regulated genes and 1 down-regulated gene were identified as central genes and acted as important prognostic roles in gastric cancer. 17 miRNAs were confirmed that might potentially regulate the expressions of these central genes. But only 8 out of them indicated better outcome in gastric cancer. Further, 79 lncRNAs were predicted that might have the potence to combine with the 8 central miRNAs. The lncRNA H19 was eventually defined as a central lncRNA by survival analyses. Stimultaneously, we found that there were certain interactions among lncRNA, miRNA and mRNAs in 50 gastric cancer tissues by qRT-PCR. Moreover, the high expression of H19 is associated with advanced TNM stage, primary tumor and lymph nodes, indicating a poor prognosis. In summary, we uncovered the prognostic value of COL3A1/FBN1/COL5A2/SPARC-mir-29a-3p-H19 ceRNA network in gastric cancer.
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BACKGROUND: Cancer/testis antigens (CTAs) are a special type of tumor antigen and are believed to act as potential targets for cancer immunotherapy. METHODS: In this study, we first screened a rational CTA MAGE-A1 for lung adenocarcinoma (LUAD) and explored the detailed characteristics of MAGE-A1 in LUAD development through a series of phenotypic experiments. Then, we developed a novel MAGE-A1-CAR-T cell (mCART) using lentiviral vector based on our previous MAGE-A1-scFv. The anti-tumor effects of this mCART were finally investigated in vitro and in vivo. RESULTS: The results showed striking malignant behaviors of MAGE-A1 in LUAD development, which further validated the rationality of MAGE-A1 as an appropriate target for LUAD treatment. Then, the innovative mCART was successfully constructed, and mCART displayed encouraging tumor-inhibitory efficacy in LUAD cells and xenografts. CONCLUSIONS: Taken together, our data suggest that MAGE-A1 is a promising candidate marker for LUAD therapy and the MAGE-A1-specific CAR-T cell immunotherapy may be an effective strategy for the treatment of MAGE-A1-positive LUAD.
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Adenocarcinoma del Pulmón/metabolismo , Neoplasias Pulmonares/metabolismo , Antígenos Específicos del Melanoma/metabolismo , Linfocitos T/metabolismo , Animales , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Células HEK293 , Humanos , Antígenos Específicos del Melanoma/genética , Ratones , Ratones Desnudos , Neoplasias Experimentales , Receptores Quiméricos de Antígenos/inmunologíaRESUMEN
Secreted protein acidic and rich in cysteine (SPARC) plays a crucial role in the malignant progression of a number of human cancers. However, the roles of SPARC in lung squamous cell carcinoma (LSCC) remain elusive. In this present study, we first detected SPARC expression and investigated the relationship between SPARC expression and the clinicopathological attributes of LSCC patients. Then we constructed SPARC-overexpression model in LSCC cell line to explore the characteristics of SPARC in LSCC development both in vitro and in vivo. The data demonstrated a remarkably higher level of SPARC in LSCC tissues than in corresponding non-cancerous tissues and elevated SPARC expression was significantly correlated with poor outcome in LSCC patients. Moreover, a serial of phenotypic experiments indicated that SPARC overexpression substantially facilitated the growth and inhibited the apoptosis in LSCC cells and xenografts. Taken together, our results suggest that SPARC is a novel prognostic marker for LSCC prognosis and SPARC significantly promotes LSCC tumorigenesis. Targeting SPARC may provide a novel therapeutic strategy for LSCC management.
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Carcinogénesis/genética , Carcinoma de Células Escamosas/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares/genética , Osteonectina/genética , Animales , Carcinogénesis/metabolismo , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Línea Celular Tumoral , Proliferación Celular/genética , Femenino , Humanos , Estimación de Kaplan-Meier , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Masculino , Ratones Endogámicos BALB C , Ratones Desnudos , Persona de Mediana Edad , Osteonectina/metabolismo , Pronóstico , Trasplante Heterólogo , Carga Tumoral/genéticaRESUMEN
BACKGROUND: FLOT1 is a scaffolding protein of lipid rafts that is believed to be involved in numerous cellular processes. However, few studies have explored the function of FLOT1 in the development of lung adenocarcinoma (LUAD) and the underlying mechanisms of FLOT1 activity. METHODS: FLOT1 knockdown and overexpression models were constructed via lentivirus. Cell growth, invasion, migration, and apoptosis were detected to evaluate the role of FLOT1 in LUAD development. Epithelial-mesenchymal transition (EMT) and cell cycle regulatory markers were then examined. Finally, the influence of FLOT1 on the Erk/Akt signaling pathway was investigated. RESULTS: FLOT1 promoted cell growth, invasion, and migration and inhibited cell apoptosis. In addition, FLOT1 induced EMT and modulated the cell cycle by activating the Erk/Akt signaling pathway. CONCLUSION: The findings indicate a significant role of FLOT1 in LUAD development. Targeting FLOT1 may be a potential therapeutic strategy for LUAD.
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Adenocarcinoma del Pulmón/genética , Neoplasias Pulmonares/genética , Sistema de Señalización de MAP Quinasas , Proteínas de la Membrana/genética , Células A549 , Adenocarcinoma del Pulmón/metabolismo , Ciclo Celular , Proliferación Celular , Transición Epitelial-Mesenquimal , Regulación Neoplásica de la Expresión Génica , Técnicas de Silenciamiento del Gen , Humanos , Neoplasias Pulmonares/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de SeñalRESUMEN
The receptor-tyrosine-kinase (RTK)-like orphan receptor 1 (ROR1) is a transmembrane glycoprotein regarded as a tumor-associated antigen. ROR1 plays an important role in cancer development, but the detailed function of ROR1 in diffuse large B-cell lymphoma (DLBCL) remains unclear. In this study, we first detected ROR1 expression and evaluated the relationship between ROR1 expression and the clinicopathological characteristics of DLBCL patients. Next we employed shRNA-mediated knockdown of ROR1 in DLBCL cell line to explore the characteristics of ROR1 in DLBCL development both in vitro and in vivo. The results showed a significantly higher level of ROR1 in DLBCL tissues than in lymphatic hyperplasia tissues. High ROR1 expression was correlated with unfavorable prognosis in DLBCL patients. Furthermore, ROR1 knockdown inhibited the growth and induced the apoptosis in DLBCL cells and xenografts. In addition, shROR1 inhibited activation of the PI3K/Akt/mTOR signaling pathway, both in vitro and in vivo. Taken together, our results suggest that ROR1 is a novel prognostic marker for DLBCL survival and ROR1 significantly promotes DLBCL tumorigenesis by regulating the PI3K/Akt/mTOR signaling pathway. Targeting ROR1 may provide a promising strategy for DLBCL treatment. © 2019 BioFactors, 45(3):416-426, 2019.
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Linfoma/metabolismo , Linfoma/patología , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Receptores Huérfanos Similares al Receptor Tirosina Quinasa/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Animales , Regulación Neoplásica de la Expresión Génica/genética , Regulación Neoplásica de la Expresión Génica/fisiología , Humanos , Ratones Endogámicos BALB C , Ratones Desnudos , Fosfatidilinositol 3-Quinasas/genética , Proteínas Proto-Oncogénicas c-akt/genética , Receptores Huérfanos Similares al Receptor Tirosina Quinasa/genética , Transducción de Señal/genética , Transducción de Señal/fisiología , Serina-Treonina Quinasas TOR/genética , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
While the application of early screening and HPV vaccines has reduced the incidence and mortality rates of cervical cancer, it remains the third most common carcinoma and fourth leading cause of cancer-associated death among women worldwide. The precise mechanisms underlying progression of cervical cancer are not fully understood at present. Here, we detected significant down-regulation of 15-hydroxyprostaglandin dehydrogenase (HPGD) in cervical cancer tissues. Overexpression of HPGD inhibited cervical cancer cell proliferation, migration and anchorage-independent growth to a significant extent. To clarify the mechanisms underlying HPGD down-regulation in cervical cancer, miRNA microarray, bioinformatics and luciferase reporter analyses were performed. HPGD was identified as a direct target of miR-146b-3p displaying up-regulation in cervical cancer tissues. Similar to the effects of HPGD overexpression, down-regulation of miR-146b-3p strongly suppressed proliferation, migration and anchorage-independent growth of cervical cancer cells. Furthermore, HPGD negatively regulated activities of STAT3 and AKT that promote cervical cancer cell proliferation. Notably, HPV oncogenes E6 and E7 were determined as potential contributory factors to these alterations. Our results collectively suggest that the HPGD/miR-146b-3p axis plays a significant role in cervical cancer and may serve as a potentially effective therapeutic target.
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Regulación Neoplásica de la Expresión Génica , Hidroxiprostaglandina Deshidrogenasas/genética , MicroARNs/genética , Infecciones por Papillomavirus/genética , Proteínas Proto-Oncogénicas c-akt/genética , Factor de Transcripción STAT3/genética , Neoplasias del Cuello Uterino/genética , Secuencia de Bases , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Progresión de la Enfermedad , Femenino , Células HEK293 , Células HeLa , Interacciones Huésped-Patógeno/genética , Papillomavirus Humano 16/genética , Papillomavirus Humano 16/patogenicidad , Papillomavirus Humano 18/genética , Papillomavirus Humano 18/patogenicidad , Humanos , Hidroxiprostaglandina Deshidrogenasas/metabolismo , MicroARNs/metabolismo , Proteínas Oncogénicas Virales/genética , Proteínas Oncogénicas Virales/metabolismo , Proteínas E7 de Papillomavirus/genética , Proteínas E7 de Papillomavirus/metabolismo , Infecciones por Papillomavirus/metabolismo , Infecciones por Papillomavirus/patología , Infecciones por Papillomavirus/virología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Represoras/genética , Proteínas Represoras/metabolismo , Factor de Transcripción STAT3/metabolismo , Transducción de Señal , Neoplasias del Cuello Uterino/metabolismo , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/virologíaRESUMEN
Lung adenocarcinoma is the most common subtype of non-small cell lung cancer and responsible for more than 500,000 deaths per year worldwide. In this study, we aimed to explore the effects of COPB2 in the progression of lung adenocarcinoma and its underlying mechanism. The mRNA and protein levels of COPB2 in tumor tissues and cell lines were determined by qRT-PCR and western blotting analysis. siRNAs and over-expressed vector targeting COPB2 were used to down-regulate and up-regulate COPB2 expression in lung adenocarcinoma cell lines H1975. Cell apoptosis rate, proliferation and tumorigenesis of H1975 cells were determined by flow cytometry analysis, MTT assay and in vivo xenotransplantation assay, respectively. Western blotting and immunofluorescence assays were performed to evaluate the effects of COPB on the expression and subcellular location of YAP. Results showed COPB2 was significantly up-regulated in lung adenocarcinoma tissues and cell lines, which showed a close correlation with advanced clinical symptoms, such as tumor differentiation, TNM stage and the occurrence of lymph node metastasis and distance metastasis. Besides, the overall survival time of patients with high expression of COPB2 was shorter than that of patients with low COPB2 expression. After knockdown of COPB2, cell apoptosis rate was increased, whereas cell proliferation was decreased. Compared with that in the normal lung cell line H1688 cells, YAP1 expression was obviously increased in H1975, and over-expression of COPB2 translocated YAP1 from cytoplasm to nuclear, whereas knockdown of COPB2 showed the opposite effect. Overexpression of COPB2 enhanced cell proliferation, tumorigenesis and inhibited cell apoptosis. However, these effects were abolished when down-regulated YAP1 expression on the base of COPB2 over-expression. In conclusion, the increased expression of COPB2 was significantly correlated with the progression of lung adenocarcinoma. Up-regulation of COPB2 inhibited cell apoptosis and promoted cell growth and tumorigenesis through up-regulating YAP1 expression in lung adenocarcinoma.
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Proteínas Adaptadoras Transductoras de Señales/biosíntesis , Adenocarcinoma/metabolismo , Carcinogénesis/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Proteína Coatómero/biosíntesis , Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares/metabolismo , Fosfoproteínas/biosíntesis , Células A549 , Proteínas Adaptadoras Transductoras de Señales/genética , Adenocarcinoma/genética , Adenocarcinoma/patología , Adenocarcinoma del Pulmón , Anciano , Animales , Carcinogénesis/genética , Carcinogénesis/patología , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Proliferación Celular/fisiología , Proteína Coatómero/genética , Femenino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Persona de Mediana Edad , Fosfoproteínas/genética , Factores de Transcripción , Regulación hacia Arriba/fisiología , Ensayos Antitumor por Modelo de Xenoinjerto/métodos , Proteínas Señalizadoras YAPRESUMEN
Circular RNAs (circRNAs) are a group of non-protein-coding RNAs that are generated from back-splicing. Recent evidence indicates that circRNAs play important roles in tissue development, gene regulation, and carcinogenesis. It was recently demonstrated that circular RNAs can function as sponges for miRNAs. In our study, the clinical implications of circRNF13 were assessed in 50 pathologically diagnosed lung adenocarcinoma samples and their paired peripheral normal lung tissues by using quantitative polymerase chain reaction. We validated that circRNF13 was almost 2.98-fold down-regulated in cancer tissues. The expression level of circRNF13 was significantly negatively correlated with TNM staging and lymph node metastasis. In vitro experiments indicated that circRNF13 repressed the invasion and metastasis of lung adenocarcinoma cell lines. Cell fraction analyses and fluorescence in situ hybridization detected that circRNF13 was mostly located in the cytoplasm. Bioinformatic analyses and RIP experiments revealed that circRNF13 could interact with Ago2, an RNA binding protein, and could function as sponge for miR-93-5p. Our data suggest that circRNF13 represents a potential novel biomarker and a therapeutic target of lung adenocarcinoma.
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Adenocarcinoma del Pulmón/genética , Regulación hacia Abajo , Neoplasias Pulmonares/genética , MicroARNs/genética , ARN/genética , Células A549 , Anciano , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Metástasis de la Neoplasia , Pronóstico , ARN Circular , Análisis de SupervivenciaRESUMEN
BACKGROUND AND OBJECTIVE: N-myc downstream-regulated gene 3 (NDRG3) is one of the important members of the NDRG family which crucially take part in cell proliferation, differentiation and other biological processes. METHODS: In this present study, western-blotting analysis was performed to evaluate NDRG3 expression in NSCLC cell lines. One-step quantitative reverse transcription-polymerase chain reaction (qPCR) with 16 fresh-frozen NSCLC samples and immunohistochemistry (IHC) analysis in 100 NSCLC cases were conducted to explore the relationship between NDRG3 expression and the clinicopathological characteristics of NSCLC. RESULTS: NDRG3 expression levels were statistically higher in NSCLC cell lines and tissue samples, compared with that of in non-cancerous cell line and tissue samples (p< 0.05). The IHC data demonstrated that the NDRG3 expression was significantly correlated with pathological grade (p= 0.038), N (p= 0.020) and TNM stage (p= 0.002). Survival analysis and Kaplan-Meier curve indicated that NDRG3 expression (p= 0.002) and T (p= 0.047) were independently associated with the unfavorable overall survival of patients with NSCLC. CONCLUSIONS: The data implied that NDRG3 expression may be identified as a new predictor in NSCLC prognosis.
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Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Neoplasias Pulmonares/metabolismo , Proteínas del Tejido Nervioso/biosíntesis , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/biosíntesis , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Femenino , Humanos , Péptidos y Proteínas de Señalización Intracelular , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , Pronóstico , Análisis de SupervivenciaRESUMEN
Rab27b is reported to associate with the development and progression of several types of human cancers. However, the relationship between Rab27b expression and the clinical characteristics of lung adenocarcinoma (LUAD) is rarely explored. In this present study, the TCGA database was consulted, followed by one-step quantitative reverse transcription polymerase chain reaction (qPCR), Western blot, and immunohistochemistry (IHC) analyses in LUAD cell lines and tissue samples. Rab27b expression levels were statistically higher in LUAD cell lines and tissue samples compared with a noncancerous cell line and tissue samples (p < 0.05). Rab27b expression was statistically correlated with lymph node metastasis (p = 0.016) and TNM stage (p = 0.019). Survival analysis and Kaplan-Meier curve revealed that Rab27b expression (p = 0.006) and TNM stage (p = 0.027) were independently associated with the unfavorable overall survival of patients with LUAD. These results indicate that high expression of Rab27b correlates with malignant attributes of LUAD and Rab27b may be identified as a potential indicator of metastasis and prognosis for LUAD.
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Adenocarcinoma del Pulmón/patología , Neoplasias Pulmonares/patología , Metástasis Linfática/patología , Proteínas de Unión al GTP rab/genética , Proteínas de Unión al GTP rab/metabolismo , Células A549 , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/metabolismo , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Línea Celular Tumoral , Progresión de la Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Metástasis Linfática/genética , Masculino , Estadificación de Neoplasias , Pronóstico , Análisis de Supervivencia , Regulación hacia ArribaRESUMEN
BACKGROUND: To evaluate the clinical efficacy and toxicity of single pemetrexed treatment compared with platinum-based pemetrexed doublet pemetrexed-based as first-line treatment for advanced nonsquamous nonsmall cell lung cancer (NS-NSCLC) in elderly Chinese patients. METHODS: The study retrospectively reviewed 175 elderly Chinese patients with NS-NSCLC from June 2010 to September 2013: 90 patients received single pemetrexed treatment, 45 received pemetrexed plus oxaliplatin, and 40 received pemetrexed plus carboplatin. Clinical efficacy was assessed using disease control rate (DCR), overall survival (OS), and progression-free survival (PFS). RESULTS: DCR, OS, and PFS did not significantly differ between single pemetrexed treatment (OS: 14.9 months; DCR: 62.2%; PFS: 3.3 months), pemetrexed plus oxaliplatin (OS: 16.5 months; DCR: 71.1%; PFS: 4.5 months), and pemetrexed plus carboplatin (OS: 15.5 months; DCR: 70.0%; PFS: 4.6 months) groups. Pemetrexed treatment caused significantly lower incidences of adverse events, such as hepatotoxicity and peripheral nerve injury. Performance status (PS), TNM stage, and Thymidylate synthase (TS) expression were predictive factors of DCR. Pemetrexed chemotherapy cycles, PS, and TNM stage were independent prognostic factors. CONCLUSIONS: Single pemetrexed was noninferior to platinum-based pemetrexed doublet for clinical efficacy and safety in elderly Chinese patients with advanced NS-NSCLC. Chemotherapy cycles, performance status, and TNM stage were independent prognostic factors.
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Adenocarcinoma/tratamiento farmacológico , Antineoplásicos/uso terapéutico , Carcinoma de Células Grandes/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Pemetrexed/uso terapéutico , Adenocarcinoma/mortalidad , Anciano , Anciano de 80 o más Años , Carboplatino/uso terapéutico , Carcinoma de Células Grandes/mortalidad , Femenino , Humanos , Neoplasias Pulmonares/mortalidad , Masculino , Análisis Multivariante , Compuestos Organoplatinos/uso terapéutico , Oxaliplatino , Estudios RetrospectivosRESUMEN
The human oncogenic virus Kaposi's sarcoma-associated herpesvirus (KSHV) is linked to Kaposi's sarcoma (KS), a tumor of endothelial cells characterized by angiogenesis and invasiveness. KSHV genome encodes 25 mature microRNAs (miRNAs), but their roles in KSHV-induced tumor dissemination and angiogenesis are not fully understood. In this study, we constructed the sensor reporters of KSHV miRNAs and used a luciferase reporter assay to demonstrate the function of the mimics of KSHV miRNAs. Then, we examined the expression of matrix metalloproteinases (MMPs) and pro-angiogenic cytokines that are related to cell migration and angiogenesis in the KSHV 25 miRNAs transfected endothelial cells. We found that all KSHV miRNAs increased the expression of the transcripts of MMP1, MMP13, VEGFA, and VEGFR2 in different degrees, as well as the secretion of VEGFA protein in the supernatant of endothelial cells. Our results reveal that KSHV miRNAs contribute to regulating MMPs and expression of pro-angiogenic factors, thus, suggesting that these miRNAs might play a crucial role in KSHV-induced cell motility and angiogenesis.
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Citocinas/metabolismo , Células Endoteliales/virología , Herpesvirus Humano 8/genética , Metaloproteinasas de la Matriz/genética , MicroARNs/genética , ARN Viral/genética , Sarcoma de Kaposi/virología , Movimiento Celular , Células Cultivadas , Citocinas/genética , Regulación de la Expresión Génica , Genes Reporteros , Células HEK293 , Humanos , Luciferasas/genética , Metaloproteinasa 1 de la Matriz/genética , Metaloproteinasas de la Matriz/metabolismo , Neovascularización Patológica , Sarcoma de Kaposi/fisiopatología , Transfección , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
Pemetrexed continuation maintenance therapy has been proven to be beneficial for patients with advanced non-squamous non-small cell lung cancer (NSCLC). However, the eligibility criteria for maintenance treatment are too simple. This study sought to evaluate thymidylate synthase (TS) as a predicting biomarker for pemetrexed continuation maintenance treatment in NSCLC. Specimens were collected from 87 patients treated with pemetrexed continuation maintenance therapy before and after four-cycle induction chemotherapy. Real-time quantitative PCR was used to detect TS expression in tissues. The TS expression level was correlated with characteristic clinical data, radiographic response, progression-free time (PFS) and overall survival (OS). Low total TS expression (<8.47) was associated with improved PFS (median: 4.7 months vs. 3.5 months, p = 0.034) and improved OS (time from random assignment: 16.4 months vs. 11.7 months, p = 0.026; time from induction: 19.7 months vs. 14.8 months, p = 0.022). Our results indicate that in NSCLC patients treated with pemetrexed continuation maintenance therapy, low TS expression is associated with improved PFS and OS.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Timidilato Sintasa/metabolismo , Adulto , Camptotecina/administración & dosificación , Camptotecina/análogos & derivados , Carcinoma de Pulmón de Células no Pequeñas/enzimología , Carcinoma de Pulmón de Células no Pequeñas/patología , Cetuximab/administración & dosificación , Cisplatino/administración & dosificación , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Irinotecán , Neoplasias Hepáticas/enzimología , Neoplasias Hepáticas/secundario , Neoplasias Pulmonares/enzimología , Neoplasias Pulmonares/secundario , Metástasis Linfática , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Compuestos Organoplatinos/administración & dosificación , Oxaliplatino , Pemetrexed/administración & dosificación , Compuestos de Fenilurea/administración & dosificación , Pronóstico , Piridinas/administración & dosificación , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
Latent membrane protein 1 (LMP1), which is associated with the development of different types of Epstein-Barr virus (EBV) related lymphoma, has been suggested to be an important oncoprotein. In this study, a human anti-LMP1 IgG antibody (LMP1-IgG) was constructed and characterized by ELISA, western blotting (WB), affinity and immunohistochemistry (IHC) analyses. CCK-8, MTT, apoptosis assays, antibody-dependent cell-mediated cytotoxicity (ADCC) and CDC (complement-dependent cytotoxicity) assays were performed to evaluate the inhibitory effects of LMP1-IgG on extranodal nasal-type natural killer (NK)/T-cell lymphoma (ENKTL). Then, the influence of LMP1-IgG on the JAK/STAT signaling pathway was investigated. The results showed that the successfully constructed LMP1-IgG inhibited proliferation, induced apoptosis, and activated ADCC and CDC of ENKTL in a concentration- and time- dependent manner. Moreover, phosphorylation of JAK3 and STAT3 was inhibited by LMP1-IgG. Our data indicate that LMP1-IgG may provide a novel and promising therapeutic strategy for the treatment of LMP1-positive ENKTL.