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1.
Pathol Res Pract ; 233: 153850, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35367937

RESUMO

BACKGROUND: The most studied genetic polymorphisms associated with gastric cancer (GC) risk are located in protein-coding genes. However, the localization of these in long non-coding RNAs (lncRNAs) has not been fully studied. We aim to investigate the associations of Long non-coding RNA macrophage migration inhibitory factor antisense RNA1(Lnc-MIF-AS1) five polymorphisms (rs755622, rs17004044, rs2070767, rs1007889, rs2000468) with the risk and prognosis of GC. METHODS: A total of 844 GC patients and 871 controls were included in the study. Genotyping was carried out using polymerase chain reaction-ligase detection reaction (PCR-LDR) technology. Odds ratios (ORs) and 95% confidence intervals (CIs) generated from unconditional logistic regression, were applied to quantify the effects of MIF-AS1 gene SNPs on GC risk. Log-rank test and Cox regression analysis were fitted to estimate hazard ratios (HRs) to quantify the effects of MIF-AS1 gene SNPs on GC prognosis. RESULTS: Significant associations were identified between MIF-AS1 rs17004044 variants and GC group in the codominant, dominant and additive models (OR = 2.843, P = 0.010; OR = 1.370, P = 0.004; and OR = 1.386; P = 0.001). In addition, association between rs17004044 variants and survival of GC was extremely observed (TC HR = 2.02 (1.21-3.37) P = 0.007, CC HR = 5.61 (2.12-14.83), P = 0.001). CONCLUSION: MIF-AS1 polymorphism rs17004044 contributes to increased predisposition and prognosis to GC.


Assuntos
Fatores Inibidores da Migração de Macrófagos , RNA Longo não Codificante , Neoplasias Gástricas , Humanos , Oxirredutases Intramoleculares/genética , Fatores Inibidores da Migração de Macrófagos/genética , Polimorfismo de Nucleotídeo Único/genética , Prognóstico , RNA Longo não Codificante/genética , Neoplasias Gástricas/genética
2.
Cell Death Discov ; 8(1): 20, 2022 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-35017465

RESUMO

Gastric cancer (GC) is a global health problem and further studies of its molecular mechanisms are needed to identify effective therapeutic targets. Although some long noncoding RNAs (lncRNAs) have been found to be involved in the progression of GC, the molecular mechanisms of many GC-related lncRNAs remain unclear. In this study, a series of in vivo and in vitro assays were performed to study the relationship between FAM225A and GC, which showed that FAM225A levels were correlated with poor prognosis in GC. Higher FAM225A expression tended to be correlated with a more profound lymphatic metastasis rate, larger tumor size, and more advanced tumor stage. FAM225A also promoted gastric cell proliferation, invasion, and migration. Further mechanistic investigation showed that FAM225A acted as a miR-326 sponge to upregulate its direct target PADI2 in GC. Overall, our findings indicated that FAM225A promoted GC development and progression via a competitive endogenous RNA network of FAM225A/miR-326/PADI2 in GC, providing insight into possible therapeutic targets and prognosis of GC.

3.
Biol Direct ; 16(1): 18, 2021 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-34670590

RESUMO

Skeletal muscle has an extraordinary regenerative capacity reflecting the rapid activation and effective differentiation of muscle stem cells (MuSCs). In the course of muscle regeneration, MuSCs are reprogrammed by immune cells. In turn, MuSCs confer immune cells anti-inflammatory properties to resolve inflammation and facilitate tissue repair. Indeed, MuSCs can exert therapeutic effects on various degenerative and inflammatory disorders based on their immunoregulatory ability, including effects primed by interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α). At the molecular level, the tryptophan metabolites, kynurenine or kynurenic acid, produced by indoleamine 2,3-dioxygenase (IDO), augment the expression of TNF-stimulated gene 6 (TSG6) through the activation of the aryl hydrocarbon receptor (AHR). In addition, insulin growth factor 2 (IGF2) produced by MuSCs can endow maturing macrophages oxidative phosphorylation (OXPHOS)-dependent anti-inflammatory functions. Herein, we summarize the current understanding of the immunomodulatory characteristics of MuSCs and the issues related to their potential applications in pathological conditions, including COVID-19.


Assuntos
COVID-19/terapia , Sistema Imunitário/fisiologia , Músculos/fisiologia , Regeneração/fisiologia , Células-Tronco/citologia , Animais , COVID-19/imunologia , Moléculas de Adesão Celular/metabolismo , Diferenciação Celular , Proliferação de Células , Humanos , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Inflamação , Fator de Crescimento Insulin-Like II/metabolismo , Interferon gama/metabolismo , Ácido Cinurênico/metabolismo , Cinurenina/metabolismo , Macrófagos/metabolismo , Camundongos , Músculos/metabolismo , Fosforilação Oxidativa , Receptores de Hidrocarboneto Arílico/metabolismo , Triptofano/química , Fator de Necrose Tumoral alfa/metabolismo
4.
Cancer Biomark ; 32(2): 189-198, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34057136

RESUMO

BACKGROUND: Genetic polymorphisms are believed to represent a key aspect of predisposition to gastric cancer (GC). Therefore, considering the important role of Cathepsin B (CTSB) in promoting cancer onset and development, it could be very worthful to explore the function of CTSB-related genetic polymorphisms in GC. OBJECTIVE: In this study, we investigated the correlation of CTSB-related polymorphisms (rs9009A>T, rs6731T>C, rs1293303G>C, rs1874547C>T, rs3779659C>T, rs17814426C>T and rs148669985C>T) with GC risk and prognosis in a case-control study of 994 cases and 1000 controls. METHODS: All tag single nucleotide polymorphisms (SNPs) were genotyped by polymerase chain reaction-ligase detection reaction (PCR-LDR) sequencing technology. RESULTS: The results indicated rs9009, rs6731 and rs17814426 correlated with decreased risks of GC (HR = 0.97, p< 0.001; HR = 0.86, P= 0.019; HR = 0.85, P= 0.017; respectively). Stratification analysis further showed rs17814426 variant genotypes correlated with earlier T stage (p= 0.044). In addition, GC patients carrying the C allele of rs6371 had better overall prognosis (HR = 0.62, 95%CI = 0.44-0.88). CONCLUSION: Our results firstly suggested the importance of CTSB-related polymorphisms on GC which could predict GC risk and prognosis.


Assuntos
Biomarcadores Tumorais/genética , Catepsina B/genética , Predisposição Genética para Doença , Neoplasias Gástricas/genética , Idoso , Estudos de Casos e Controles , China/epidemiologia , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Polimorfismo de Nucleotídeo Único , Prognóstico , Estômago/patologia , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia
5.
Front Mol Biosci ; 8: 655580, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33937336

RESUMO

MicroRNAs (miRNAs) are emerging as significant regulators of the tumorigenesis of gastric cancer (GC), and may be effective biomarkers for diagnosis, prognosis, and therapeutic targeting for GC. In this study, miR-653-5p was found to be significantly upregulated in GC tissues, serum, and cell lines and was strongly associated with poor prognosis in patients with GC. Furthermore, miR-653-5p promoted GC cell proliferation and metastasis in vivo and in vitro. Suppressor of cytokine signaling 6 (SOCS6) was directly targeted by miR-653-5p, and SOCS6 attenuated miR-653-5p-mediated GC cell growth, migration, and invasion. In addition, SOCS6-mediated inactivation of the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway was also reversed by the administration of miR-653-5p. The findings from this study support a novel regulatory axis between miR-653-5p, SOCS6, and JAK2/STAT3 that may be a target for diagnosis and therapeutic intervention for GC.

6.
Genomics ; 113(4): 1754-1760, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33865958

RESUMO

The most studied genetic polymorphisms associated with gastric cancer (GC) risk are located in protein-coding genes. However, these sited in long noncoding RNA (lncRNA) are not adequately explored yet. Here, we designed a case-control study of 848 cases and 880 controls to investigate the associations of polymorphisms (rs61396151, rs1059307, rs11961028, rs9351065) in lncRNA SNHG5 with the risk and prognosis of GC. The results indicate rs61396151 associated with decreased risk of GC (OR = 0.78, 95% CI = 0.62-0.96), but there were no correlations observed with the clinicopathological features of GC (P > 0.05). However, the CA genotype of rs61396151 was correlated with poor overall survival rate in a multivariate cox regression model (HR = 1.91, P = 0.040), but it was reversed with adjustment for age, gender and TNM stage (HR = 1.35, P = 0.213). Collectively, our results highlight the importance of SNHG5-related polymorphisms to GC susceptibility and prognosis.


Assuntos
RNA Longo não Codificante , Neoplasias Gástricas , /genética , Estudos de Casos e Controles , China , Predisposição Genética para Doença , Humanos , Polimorfismo Genético , Prognóstico , RNA Longo não Codificante/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia
7.
Cell Death Dis ; 11(7): 521, 2020 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-32647147

RESUMO

Gastric cancer (GC) has been one of the most leading cause of cancer-death worldwide. Long non-coding RNAs (lncRNAs) have been found to be related with the carcinogenesis and the development of various cancers, including GC. However, there are still many GC-related lncRNAs functional roles and molecular mechanisms that have not yet been clearly studied. Herein, we report lncRNA CCDC144NL-AS1, which has not been explored in GC, and it is markedly upregulated in GC tissues, which may serve as an independent predictor of poor prognosis. We found that CCDC144NL-AS1 expression was significantly positively associated with a larger tumor size and more pronounced lymph node metastasis. Through a series of in vivo and in vitro functional experiments, we observed that CCDC144NL-AS1 could facilitate cell proliferation, invasion and migration and inhibit cell apoptosis in GC. Further mechanism investigation revealed that CCDC144NL-AS1 acted as a competing endogenous RNA (ceRNA) for sponging miR-143-3p and upregulated the expression of its direct endogenous target MAP3K7 in GC. Taken together, our results elucidate the oncogenic roles of CCDC144NL-AS1/miR-143-3p/MAP3K7 axis in GC progression, providing inspiration for further understanding of the mechanism of GC and making CCDC144NL-AS1 as a potential novel diagnostic and therapeutic target for GC.


Assuntos
MAP Quinase Quinase Quinases/metabolismo , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , RNA Interferente Pequeno/metabolismo , Neoplasias Gástricas/metabolismo , Animais , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Progressão da Doença , Células HEK293 , Xenoenxertos , Humanos , MAP Quinase Quinase Quinases/genética , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , Pessoa de Meia-Idade , RNA Interferente Pequeno/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Transfecção , Regulação para Cima
8.
Oncogenesis ; 9(3): 29, 2020 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-32123162

RESUMO

Long noncoding RNAs (lncRNAs) are emerging as important regulators of tumorigenesis and are frequently dysregulated in cancers. Here, we identify a critical lncRNA TRPM2-AS which is aberrantly expressed in gastric cancer (GC) tissues by screening The Cancer Genome Atlas Program(TCGA) database of GC cohort, and its upregulation is clinically associated with advanced pathologic stages and poor prognosis in GC patients. Silencing TRPM2-AS inhibits the proliferation, metastasis and radioresistance of GC cell whereas ectopic expression of TRPM2-AS significantly improves the progression of GC cell in multiple experiments. Mechanistically, TRPM2-AS serves as a microRNA sponge or a competitive endogenous RNA (ceRNA) for tumor suppressive microRNA miR-612 and consequently modulates the derepression of IGF2BP1 and FOXM1. Moreover, induced upregulation of IGF2BP1 subsequently increases the expression of c-Myc and promotes GC cell progression. Meanwhile, TRPM2-AS promotes the radioreistance of GC cell through enhancing the expression of FOXM1 as well. Thus, our findings support a new regulatory axis between TRPM2-AS, miR-612, IGF2BP1, or FOXM1 which serve as crucial effectors in GC tumorigenesis and malignant development, suggesting a promising therapeutic and diagnostic direction for GC.

9.
J Exp Clin Cancer Res ; 38(1): 452, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31694721

RESUMO

BACKGROUND: Increasing evidence shows that stimulated by retinoic acid 6 (STRA6) participates in regulating multiple cancers. However, the biological roles of STRA6 in gastric cancer (GC) remain unknown. This study aimed to investigate the biological function of STRA6 and reveal the underlying mechanism of its dysregulation in GC. METHODS: The expression level of STRA6 was detected through quantitative real-time PCR and Western blot analysis. The effects of STRA6 on the proliferation of GC cells were studied through CCK-8 proliferation, colony formation and 5-ethynyl-2'-deoxyuridine (EdU) assays. The effects of STRA6 on migration and invasion were detected via wound healing and Transwell assays. Upstream miRNAs, which might regulate STRA6 expression, was predicted through bioinformatics analysis. Their interaction was further confirmed through dual-luciferase reporter assays and rescue experiments. RESULTS: STRA6 was up-regulated in GC and enhanced the proliferation and metastasis of GC cells in vitro and in vivo. STRA6 knockdown could inhibit the Wnt/ß-catenin signalling pathway. STRA6 was confirmed as an miR-873 target, which acted as a tumour suppressor in GC. Rescue assays showed that the repressing effect of miR-873 could be partially reversed by overexpressing STRA6. CONCLUSIONS: STRA6 is down-regulated by miR-873 and plays an oncogenic role by activating Wnt/ß-catenin signalling in GC.


Assuntos
Transformação Celular Neoplásica/genética , Regulação Neoplásica da Expressão Gênica , Proteínas de Membrana/genética , MicroRNAs/genética , Oncogenes , Interferência de RNA , Neoplasias Gástricas/etiologia , Regiões 3' não Traduzidas , Adulto , Idoso , Animais , Biomarcadores Tumorais , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Proteínas de Membrana/metabolismo , Camundongos , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Carga Tumoral , Via de Sinalização Wnt
10.
Artif Cells Nanomed Biotechnol ; 47(1): 3814-3822, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31549851

RESUMO

It was investigated that TP73-AS1(TP73 antisense RNA 1) could function as an oncogene in gastric cancer (GC). The expression and function of long noncoding RNAs (lncRNAs) could be impacted by single nucleotide polymorphisms (SNPs), which are related to cancer susceptibility and prognosis. This study was to reveal the association between lncRNAs TP73-AS1 polymorphisms (rs1181865 A > G, rs9800 G > C, rs3737589 A > G, rs2298222 G > A, rs7515164 C > A) and GC in 1000 GC cases and 1000 controls in a Chinese Han population. Rs3737589 G allele had significant associations with the increasing risk of GC (G vs. A: p = .005). Rs3737589 variant genotypes (AG + GG) were related to an increased risk of GC in the elder population (age ≥60), females, nonsmokers, nondrinkers, individuals living in urban, and individuals without family history of GC in stratified analyses. Rs3737589 variant genotypes (AG + GG) were related to the advanced depth of tumor invasion (T3 + T4). Besides, we found that GC patients with AG or GG genotype of rs3737589 had poorer overall survival (OS) than those with AA genotype (p < .05). Our findings showed that the lncRNA TP73-AS1 rs3737589 polymorphism might increase the risk of GC, and rs3737589 polymorphism could be a potential biomarker to predict the prognosis of GC patients.


Assuntos
/genética , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único , RNA Longo não Codificante/genética , Neoplasias Gástricas/genética , Estudos de Casos e Controles , China/epidemiologia , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patologia , Análise de Sobrevida
11.
BMC Cardiovasc Disord ; 18(1): 157, 2018 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-30064376

RESUMO

BACKGROUND: The aim of the study was to investigate the high-sensitivity troponin T (hs-TnT) release profile in off-pump coronary artery bypass grafting (OPCABG) patients with normal postoperative course. METHODS: From January 2015 to October 2016, 398 consecutive OPCABG patients who had normal postoperative courses were enrolled. Blood samples for hs-TnT were collected at several time points and the comparisons among different time points grouped by various factors were further analyzed. RESULTS: There were 317 male and 81 female patients, with a median age of 64. For 66.1% of the patients, peak hs-TnT occurred at the 24th hour after OPCABG, regardless of the groups divided by different factors. In total, the hs-TnT values were much higher in male group (P = 0.035), in patients who need 5 or more bypass grafts (P = 0.035) and in patients with high-risk EuroSCORE II assessment (P = 0.013). However, we failed to find any significant differences between different age groups (P = 0.129) or among different coronary heart disease classifications (P = 0.191). CONCLUSIONS: The hs-TnT values were affected by various factors and culminated around the first 24 h following OPCABG. It may provide some useful information for future clinical studies of myocardial biomarkers after OPCABG.


Assuntos
Ponte de Artéria Coronária sem Circulação Extracorpórea , Doença da Artéria Coronariana/cirurgia , Troponina T/sangue , Biomarcadores/sangue , Ponte de Artéria Coronária sem Circulação Extracorpórea/efeitos adversos , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Resultado do Tratamento , Regulação para Cima
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