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BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a predominant subtype of esophageal cancer with relatively high mortality worldwide. Serine peptidase inhibitor Kazal-type 5 (SPINK5) is reported to be downregulated in ESCC. However, its explicit role in ESCC remains further investigation. METHODS: The tumor tissues and adjacent non-cancerous tissues were obtained from 196 patients with ESCC for the determination of SPINK5 mRNA levels. Additionally, the relationship between SPINK5 mRNA levels and clinicopathological features of ESCC patients was explored. The effects of SPINK5 on the invasion and migration of ESCC cells were assessed using Transwell assays. Furthermore, SPINK5 mRNA and LEKTI protein were measured in ESCC cell lines after treatment with poly (I:C), lipopolysaccharide (LPS) or unmethylated CpG DNA. Moreover, the correlation between expression of SPINK5 and nuclear factor-kappa B (NF-κB) signaling pathway-related genes was analyzed in the TCGA-ESCC cohort, and the effects of SPINK5 on NF-κB transcription was analyzed using a luciferase reporter gene assay. Finally, the correlations between SPINK5 and infiltration of immune cells, immune scores, stromal scores and ESTIMATE (i.e., Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data) scores were explored. RESULTS: SPINK5 mRNA levels were downregulated in tumor tissues, which was significantly correlated with higher lymph node metastases. Overexpressed SPINK5 inhibited cell invasion and migration in ESCC cell lines. Mechanistically, LPS-induced activation of Toll-like receptor 4 (TLR4) decreased SPINK5 mRNA and LEKTI in KYSE150 and KYSE70 cells. Spearman correlation analysis revealed that SPINK5 mRNA was significantly negatively correlated with a total of seven NF-κB signaling pathway-related genes in TCGA-ESCC patients. Moreover, downregulation of SPINK5 increased and upregulation of SPINK5 decreased the activity of the NF-κB promoter in HEK293T cells. Finally, immune cells infiltration analysis revealed that SPINK5 was significantly correlated with the infiltration of various immune cells, stromal scores, immune scores and ESTIMATE scores. CONCLUSIONS: SPINK5 plays critical roles in the TLR4/NF-κB pathway and immune cells infiltration, which might contribute to the ESCC metastasis. The findings of the present study may provide a promising biomarker for the diagnosis and treatment of esophageal squamous cell carcinoma.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Inibidor de Serinopeptidase do Tipo Kazal 5 , Humanos , Neoplasias Esofágicas/imunologia , Neoplasias Esofágicas/metabolismo , Carcinoma de Células Escamosas do Esôfago/imunologia , Carcinoma de Células Escamosas do Esôfago/metabolismo , Células HEK293 , Lipopolissacarídeos , NF-kappa B/metabolismo , RNA Mensageiro/metabolismo , Inibidor de Serinopeptidase do Tipo Kazal 5/metabolismo , Receptor 4 Toll-Like/metabolismoRESUMO
BACKGROUND: Lung adenocarcinoma (LUAD) is a leading cause of tumor-associated mortality, and it is needed to find new target to combat this disease. Guanine nucleotide-binding -protein-like 3 (GNL3) mediates cell proliferation and apoptosis in several cancers, but its role in LUAD remains unclear. OBJECTIVE: To explore the expression and function of Guanine nucleotide-binding protein-like 3 (GNL3) in lung adenocarcinoma (LUAD) and its potential mechanism in inhibiting the growth of LUAD cells. METHODS: We evaluated the expression of GNL3 in LUAD tissues and its association with patient prognosis using databases and immunohistochemistry. Cell proliferation was assessed by CCK-8 assay as well as colony formation, while apoptosis was evaluated by FCM. The effect of GNL3 knockdown on the Wnt/ß-catenin axis was investigated by Immunoblot analysis. RESULTS: GNL3 is overexpressed in LUAD tissues and is correlated with poor prognosis. Knockdown of GNL3 significantly inhibited the growth as well as induced apoptosis in A549 as well as H1299 cells. Furthermore, we found that the inhibitory effect of GNL3 knockdown on LUAD cell growth is associated with the downregulation of the Wnt/ß-catenin axis. CONCLUSION: GNL3 is key in the progression of LUAD by metiating Wnt/ß-catenin axis. Targeting GNL3 may represent a novel therapeutic method for LUAD treatment.
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Adenocarcinoma de Pulmão , Apoptose , Proliferação de Células , Técnicas de Silenciamento de Genes , Neoplasias Pulmonares , Via de Sinalização Wnt , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/genética , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/metabolismo , Linhagem Celular Tumoral , Prognóstico , Proteínas de Ligação ao GTP/metabolismo , Proteínas de Ligação ao GTP/genética , beta Catenina/metabolismo , Regulação Neoplásica da Expressão Gênica , Células A549 , Proteínas NuclearesRESUMO
OBJECTIVE: To detect the expression of RING finger protein 135 (RNF135) in lung adenocarcinoma tissues and explore its role in the progression of lung adenocarcinoma. METHODS: Bioinformation analysis, quantitative polymerase chain reaction, and immunoblotting technique discovered the expression of RNF135 in lung adenocarcinoma tissues. Cell counting kit-8 and colony formation, immunostaining, and immunoblot assays examined the effects of RNF135 on cell growth and autophagy. Co-immunoprecipitation (Co-IP), immunostaining, and immuoblotting were conducted to confirm the mechanism. RESULTS: RNF135 was highly expressed in lung adenocarcinoma. In addition, RNF135 promoted lung adenocarcinoma cell growth. Further, data confirmed that RNF135 promoted autophagy in lung adenocarcinoma cells. Mechanically, RNF135 directly interacted with Unc-51-like autophagy activating kinase 1 (ULK1) to promote its phosphorylation level. CONCLUSION: RNF135 promoted cell growth and autophagy in lung adenocarcinoma by promoting the phosphorylation of ULK1.
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Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Ubiquitina-Proteína Ligases , Humanos , Autofagia , Proteína Homóloga à Proteína-1 Relacionada à Autofagia/metabolismo , Proliferação de Células , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/farmacologia , Neoplasias Pulmonares/patologia , Fosforilação , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/farmacologiaRESUMO
The aim of this research was to investigate the role of hyaluronan-binding protein 1 (HABP1) in lung adenocarcinoma. It was demonstrated by bioinformatics analysis that HABP1 was one of the differentially expressed genes in lung adenocarcinoma. Then, it was confirmed by qPCR, western blot, and immunohistochemistry analysis that HABP1 was upregulated in human tissue specimens we collected. Survival analysis showed that HABP1 was promised to serve as a new biomarker to predict the progress and prognosis of lung adenocarcinoma patients. In addition, we further studied the effects of regulating the expression of HABP1 on lung adenocarcinoma cells, indicating that altered expression of HABP1 could adjust cell proliferation and invasion through the NFκB signaling pathway.
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Adenocarcinoma de Pulmão , Proteínas Mitocondriais , Adenocarcinoma de Pulmão/genética , Proteínas de Transporte , Proliferação de Células , Humanos , Proteínas Mitocondriais/metabolismo , PrognósticoRESUMO
BACKGROUND: In unresectable hepatocellular carcinoma (HCC), methods to predict patients at increased risk of progression are required. PURPOSE: To investigate the feasibility of radiomics model in predicting early progression of unresectable HCC after transcatheter arterial chemoembolization (TACE) therapy using preoperative multiparametric magnetic resonance imaging (MP-MRI). STUDY TYPE: Retrospective. POPULATION: A total of 84 patients with BCLC B stage HCC from one medical center. According to the modified response evaluation criteria in solid tumors, patients who progressed at 6 months after TACE therapy were assigned as the progressive disease (PD) group (n = 32). Patients whose MRI was performed on four devices were divided into a training cohort (n = 67). Patients whose MRI was performed on other than the previous four devices were used as the testing set (n = 17). FIELD STRENGTH/SEQUENCE: 3.0T, 1.5T axial T2 -weighted imaging (T2 WI), diffusion-weighted imaging (DWI, b = 0, 500 s/mm2 ), and apparent diffusion coefficient (ADC) ASSESSMENT: PD was confirmed via imaging studies with MRI. Risk factors, including age, alpha fetoprotein (AFP), size, and radiomic-related features of PD were assessed. In addition, the discrimination ability of each radiomics signature was tested on an independent testing set. STATISTICAL TESTS: The area under the receiver-operator characteristic (ROC) curve (AUC) was used to evaluate the predictive accuracy of the radiomic signature in both the training and testing sets. The results indicated that the MP-MRI model achieved the greatest benefit. RESULTS: In the testing set, the model based on DWI features presented an AUC of (b = 0, 0.786; b = 500, 0.729), followed by T2 WI features (0.729) and ADC (0.714). The AUC of the MP-MRI signature was increased to 0.800 compared to any single MRI signature. The multivariate logistic analysis identified the radiomics signature as independent parameters of PD, while clinical information such as age, AFP, size, etc., had no significance in the PD group. DATA CONCLUSION: Preoperative MP-MRI has the potential to predict the outcome of TACE therapy for unresectable HCC. In addition, these image features may be complementary to the current staging systems of HCC patients. LEVEL OF EVIDENCE: 2. TECHNICAL EFFICACY STAGE: 3. J. Magn. Reson. Imaging 2020;52:1083-1090.
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Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/terapia , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/terapia , Imageamento por Ressonância Magnética , Estudos RetrospectivosRESUMO
BACKGROUND: Lymphocyte activation gene 3 (LAG-3, also known as CD223) is an immune checkpoint molecule expressed on various types of lymphocytes, and it is mainly involved in maintaining immune homeostasis. However, there are currently no data on LAG-3 expression in non-small-cell lung cancer cells. METHODS: Human lung cancer cells were cultured using conventional methods. The expression of LAG-3 was measured by Western blot and flow cytometry. Between April 2018 and May 2019, we collected 52 surgical specimens of stage I-III non-small-cell lung cancer (NSCLC). Fourteen samples of benign lung tissue lesions were collected as the control group, and the expression levels of LAG-3 in the lung cancer cells and tissue samples were measured via immunohistochemistry. RESULTS: Western blots showed that LAG-3 was expressed in lung cancer cell lines. There was significant difference in the LAG-3 expression levels in the NSCLC cells and benign lung tissue (χ2 = 13.055, P = .0003). The LAG-3 expression level was significantly associated with the NSCLC clinical stage, and LAG-3 expression was significantly higher in stage III patients (P < .05). CONCLUSION: LAG-3 is expressed in NSCLC tumor cells. Furthermore, LAG-3 not only is expressed in tumor-infiltrating lymphocytes in NSCLC patients but also is ectopically expressed in tumor cells and associated with TNM stage.
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Antígenos CD/metabolismo , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Linhagem Celular Tumoral , Expressão Ectópica do Gene , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/cirurgia , Masculino , Taxa de Sobrevida , Proteína do Gene 3 de Ativação de LinfócitosRESUMO
BACKGROUND: Hepatocellular carcinoma (HCC) is an aggressive cancer with a poor prognosis. Effective biomarkers are necessary to predict the clinical course and outcome of patients with HCC. Wntless (Wls) is a key modulator of Wnt protein secretion and is overexpressed in various human cancers. However, the mechanism and alteration of Wls expression in HCC have not been clarified. AIMS: The aim of this study was to evaluate expression level of Wls in HCC and its clinical significance. METHODS: The levels of Wls expression were investigated in 84 HCC tissues using immunohistochemistry. RESULTS: Wls was negatively expressed in normal liver tissue and was negatively or weakly (score 0) expressed in liver cirrhosis. Twenty-eight out of 84 samples (33.3%) were negative or weakly (score 0) expressed Wls, 38 out of 84 (45.2%) moderately (1+) expressed Wls, and 18 out of 84 (21.4%) strongly (2+) expressed Wls. Wls expression was positively associated with tumor size (P = 0.005, r = 0.302), tumor TNM stage (P = 0.017, r = 0.261), AFP (P = 0.051), and HBV infection (P = 0.009, r = 0.283), and was negatively associated with differentiation (P < 0.001, r = - 0.552). No significant relationship between Wls expression and liver cirrhosis, ALT, GGT, age, sex, or tumor focality was found. CONCLUSIONS: Our data showed that Wls was differentially expressed in HCC. Statistical analysis results suggest that Wls expression might increase as HCC progresses.
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Carcinoma Hepatocelular/metabolismo , Regulação Neoplásica da Expressão Gênica/fisiologia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Neoplasias Hepáticas/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Carcinoma Hepatocelular/patologia , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Receptores Acoplados a Proteínas G/genéticaRESUMO
The lysosome inhibitors bafilomycin A1 and chloroquine have both lysosomotropic properties and autophagy inhibition ability, and are promising clinical agents to be used in combination with anticancer drugs. In order to investigate this combination effect, HepG2 cells were treated with bafilomycin A1, chloroquine, or/and doxorubicin, and their proliferative ability, induction of apoptosis, and the changes of lysosomal membrane permeabilization and mitochondrial membrane potential were studied. The results demonstrate that treatment with bafilomycin A1 or chloroquine alone at a relatively low concentration promotes the inhibitory effect of doxorubicin on cell growth and apoptosis. Further studies reveal that bafilomycin A1 and chloroquine promote lysosomal membrane permeabilization and the reduction of mitochondrial membrane potential induced by doxorubicin. Our findings suggest that bafilomycin A1 and chloroquine potentiate the anticancer effect of doxorubicin in hepatic cancer cells and that supplementation of conventional chemotherapy with lysosome inhibitors may provide a more efficient anticancer therapy.
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Antineoplásicos/farmacologia , Cloroquina/farmacologia , Doxorrubicina/farmacologia , Lisossomos/efeitos dos fármacos , Macrolídeos/farmacologia , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/fisiologia , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Células Hep G2 , Humanos , Lisossomos/fisiologia , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Potencial da Membrana Mitocondrial/fisiologiaRESUMO
The expression of EphA4 has been well documented in the development of nerve and in certain types of human cancer. Few studies of EphA4, however, have focused on breast carcinoma. In this study, a set of breast carcinomas was subjected to immunohistochemical staining. In normal luminal cells, EphA4 was weakly detected in 11 (14.3 %), moderately detected in 15 (19.5 %) and highly detected in 51 out of 77 (66.2 %) samples, while in breast carcinoma cells, EphA4 was weakly detected in 42 (54.5 %), moderately detected in 19 (24.7 %) and highly detected in 16 out of 77 (20.8 %) samples (P < 0.001). The expression of EphA4 protein was significantly reduced in 68.8 % of breast carcinoma samples comparing with normal cells. The expression of EphA4 was significantly associated with tumor grade (P = 0.003), TNM stage (P = 0.034), lymph node metastasis (P = 0.034) and Ki-67 (P < 0.001). No significant relationship was found between the expression of EphA4 and age, molecular subtypes, and HER2 status. Survival analysis showed that significant association of low expression of EphA4 in tumor cells with short overall survival (P = 0.048) and disease-free survival (P = 0.051). Our data show that EphA4 was reduced in breast carcinoma, which is associated with high grade, advanced TNM stage, lymph node metastasis, and poor outcome of patients.
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Biomarcadores Tumorais/análise , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Receptor EphA4/biossíntese , Adulto , Idoso , Neoplasias da Mama/mortalidade , Carcinoma Ductal de Mama/mortalidade , Intervalo Livre de Doença , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Metástase Linfática , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Receptor EphA4/análiseRESUMO
Soil moisture content (SMC) is one of the most important indicators influencing the exchange of energy and water among vegetation, soil, and the atmosphere. Accurate detection of soil moisture content is beneficial to improving the precision of crop yield evaluating and field management measures. In this paper, a novel method ADI (Angle Dryness Index) based on NIR-RED spectral feature space used for calculating SMC was proposed, which improved the accuracy of calculating SMC with red and near infrared band reflectance. It was found that an intermediate parameter θ in NIR-RED feature space was significantly related to SMC, and independent of vegetation coverage according to the linear decomposition of mixed pixel and the empirical correlation between SMC and red/NIR band reflectance which were achieved by previous researches. Then, ADI was proposed with the feature discovered in the paper. The mathematical expression on SMC is nonlinear, and the newton iterative method is applied to ADI for calculation SMC. Then, the newly proposed method was validated with two kinds of remote sensing imagery data (Thematic Mapper (TM) and moderate resolution imaging spectrometer (MODIS)) and the synchronous observed data in the field. Validation results revealed that the ADI- derived SMC was highly accordant with the in-situ results with high correlation (R2=0.74 with TM and R2=0.64 with MODIS data). We also calculated MPDI (Modified Perpendicular Drought Index) developed by Ghulam, which is also proposed with the red and near infrared reflectance. The result showed that the accuracy of MPDI was lower than that of ADI. The most likely reason was that ADI was insensitive to fv, but the calculation errors of fv would reduce the accuracy of SMC estimation. MODIS had a low spatial resolution, thus there may be more than two end members in a mixed pixel. In this case, the linear decomposition of mixed pixel was not applicable and the errors would finally be enlarged. ADI achieved good results in monitoring SMC in vegetated area because it was less influenced by vegetation coverage than other similar approaches. ADI only requires the satellite image data including the red and near infrared band which are available from most of the optical sensors. Therefore, it is an effective and promising method for monitoring SMC in vegetated area, and would be widely used in agriculture, meteorology, and hydrology.
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Land surface temperature (Ts) is influenced by soil background and vegetation growing conditions, and the combination of Ts and vegetation indices (Vis) can indicate the status of surface soil moisture content (SMC). In this study, Advanced Temperature Vegetation Dryness Index (ATVDI) used for monitoring SMC was proposed on the basis of the simulation results with agricultural climate model CUPID. Previous studies have concluded that Normalized Difference Vegetation Index (NDVI) easily reaches the saturation point, andLeaf Area Index (LAI) was then used instead of NDVI to estimate soil moisture content in the paper. With LAI-Ts scatter diagram established by the simulation results of CUPID model; how Ts varied with LAI and SMC was found. In the case of the identical soil background, the logarithmic relations between Ts and LAI were more accurate than the linear relations included in Temperature Vegetation Dryness Index (TVDI), based on which ATVDI was then developed. LAI-Ts scatter diagram with satellite imagery were necessary for determining the expression of the upper and lower logarithmic curves while ATVDI was used for monitoring SMC. Ts derived from satellite imagery were then transformed to the Ts-value which has the same SMC and the minimum LAI in study area with look-up table. The measured SMC from the field sites in Weihe Plain, Shanxi Province, China, and the products of LAI and Ts (MOD15A2 and MOD11A2, respectively) produced by the image derived from Moderate Resolution Imaging Spectrometer (MODIS) were collected to validate the new method proposed in this study. The validation results shown that ATVDI (R² = 0.62) was accurate enough to monitor SMC, and it achieved better result than TVDI. Moreover, ATVDI-derived result were Ts values with some physical meanings, which made it comparative in different periods. Therefore, ATVDI is a promising method for monitoring SMC in different time-spatial scales in agricultural fields.
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Soil is the loose solum of land surface that can support plants. It consists of minerals, organics, atmosphere, moisture, microbes, et al. Among its complex compositions, soil moisture varies greatly. Therefore, the fast and accurate inversion of soil moisture by using remote sensing is very crucial. In order to reduce the influence of soil type on the retrieval of soil moisture, this paper proposed a normalized spectral slope and absorption index named NSSAI to estimate soil moisture. The modeling of the new index contains several key steps: Firstly, soil samples with different moisture level were artificially prepared, and soil reflectance spectra was consequently measured using spectroradiometer produced by ASD Company. Secondly, the moisture absorption spectral feature located at shortwave wavelengths and the spectral slope of visible wavelengths were calculated after analyzing the regular spectral feature change patterns of different soil at different moisture conditions. Then advantages of the two features at reducing soil types' effects was synthesized to build the NSSAI. Thirdly, a linear relationship between NSSAI and soil moisture was established. The result showed that NSSAI worked better (correlation coefficient is 0.93) than most of other traditional methods in soil moisture extraction. It can weaken the influences caused by soil types at different moisture levels and improve the bare soil moisture inversion accuracy.
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The spatio-temporal distribution and variation of soil moisture content have a significant impact on soil temperature, heat balance between land and atmosphere and atmospheric circulation. Hence, it is of great significance to monitor the soil moisture content dynamically at a large scale and to acquire its continuous change during a certain period of time. The object of this paper is to explore the relationship between the mass moisture content of soil and soil spectrum. This was accomplished by building a spectral simulation model of soil with different mass moisture content using hyperspectral remote sensing data. The spectra of soil samples of 8 sampling sites in Beijing were obtained using ASD Field Spectrometer. Their mass moisture contents were measured using oven drying method. Spectra of two soil samples under different mass moisture content were used to construct soil spectral simulation model, and the model was validated using spectra of the other six soil samples. The results show that the accuracy of the model is higher when the mass water content of soil is below field capacity. At last, we used the spectra of three sampling points on campus of Peking University to test the model, and the minimum value of root mean square error between simulated and measured spectral reflectance was 0.0058. Therefore the model is expected to perform well in simulating the spectrum reflectance of different types of soil when mass water content below field capacity.
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BACKGROUND: RING finger protein 135 plays an important role in tumorigenesis and is associated with drug resistance. METHODS: Bioinformatics analysis showed that RNF135 was significantly differentially expressed in colorectal cancer. RT-qPCR and western blot were used to detect the expression of RNF135. Immunohistochemical analysis were used to measure the expression of RNF135 and Ki-67. RESULTS: The expression of RNF135 was up-regulated in human tissue samples and colorectal cancer and was positively correlated with Ki-67. Compared with oxaliplatin sensitive patients, RNF135 expression levels were higher in the tissue of resistant patients. The regulatory effect of RNF135 on colorectal cancer cells was further investigated in vitro. Therefore, inhibition of autophagy by down-regulating RNF135 can partially increase its susceptibility to oxaliplatin.
Assuntos
Neoplasias Colorretais , Ubiquitina-Proteína Ligases , Humanos , Oxaliplatina/farmacologia , Oxaliplatina/uso terapêutico , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Antígeno Ki-67 , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Autofagia/genética , Linhagem Celular TumoralRESUMO
Tim3 is a negative immune checkpoint molecule and plays a crucial part in tumor-induced immune suppression. Tim3 is a cell surface molecule expressed on T cells marking dysfunctional CD8+ cells in various kinds of cancers. Tim3 expression was mainly reported in tumor-infiltrating lymphocytes (TILs). There are few studies focusing on the expression of Tim3 in tumor cells. Immunohistochemistry was performed to determine Tim3 expression level. The relationships between Tim3 expression in colorectal cancer cells and in tumor-infiltrating lymphocytes and cilicopathological parameters were statistically analyzed. Tim3 was differentially detected in TILs and in colorectal cancer cells. Positive expression of Tim3 in colorectal cancer cells was associated with tumor location (P=0.001), depth of tumor invasion (P<0.001), lymph node metastasis (P=0.001), TNM stage (P=0.001), MSI (P=0.008), and Braf V600E mutation (P=0.001). On the other hand, positive expression of Tim3 in TILs was only related to depth of tumor invasion (P<0.001). Positive expression of Tim3 in both colorectal cancer cells and TILs was associated with depth of tumor invasion (P<0.001), lymph node metastasis (P=0.002), TNM stage (P=0.002), MSI (P=0.039), and Braf V600E mutation (P=0.009). Kaplan-Meier survival analysis showed that Tim3 expression in colorectal cancer and in TILs was significantly associated with patient overall survival (OS) rate (P=0.039, and 0.001). Tim3 may be a potential prognostic marker and a therapy target for colorectal cancer.
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Neoplasias Colorretais , Receptor Celular 2 do Vírus da Hepatite A , Neoplasias Colorretais/patologia , Receptor Celular 2 do Vírus da Hepatite A/genética , Humanos , Metástase Linfática/patologia , Linfócitos do Interstício Tumoral , Mutação , Estadiamento de Neoplasias , Prognóstico , Proteínas Proto-Oncogênicas B-raf/genéticaRESUMO
MiR-769-5p regulates tumor correlative genes, which plays a critical role in the progression of various types of tumor. However, the precise regulatory mechanism of miR-769-5p on nonsmall cell lung cancer (NSCLC) is unknown. This study was to discover the role and underlying mechanisms of miR-769-5p in NSCLC. MiR-769-5p expression was shown to be reduced, according to our findings. MiR-769-5p overexpression inhibited NSCLC cell proliferation while promoting NSCLC cell apoptosis. Furthermore, NSCLC cell migration and invasion were reduced when miR-769-5p was overexpressed. Furthermore, HDGF was confirmed as a miR-769-5p target gene that was negatively regulated by miR-769-5p. Furthermore, more research revealed that HDGF overexpression reduced the inhibitory effect of miR-769-5p on NSCLC cell biofunction. Finally, miR-769-5p inhibited NSCLC cell proliferation and invasion by targeting HDGF, indicating that NSCLC could benefit from miR-769-5p as a diagnostic and prognostic biomarker.
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Eph tyrosine kinase receptors and their ephrin ligands are involved in normal development and tumorigenesis. Eph receptors are frequently over expressed in a wide variety of human malignant tumors, being associated with tumor growth, invasion, angiogenesis, and metastasis. This study aimed to evaluate the clinical significance of EphB4 and its ligand of ephrinB2 protein expressions in human lung adenocarcinomas. EphB4 and ephrinB2 protein expressions were assessed immunohistochemically on paraffin embedded tissues obtained from 93 patients with lung adenocarcinoma. Fifty-one out of 93 (54.8%) specimens were negative for EphB4 expression, and 42 out of 93 (45.2%) were positive for EphB4 expression. EphrinB2 expression was consistently negative in all tissues. EphB4 expression was significantly associated with tumor differentiation (P = 0.001), lymph node metastasis (P = 0.021), and Ki67 (P = 0.012). No significant relationship was found between EphB4 expression and gender, age, or ALK mutation. Our data show that EphB4 is differentially expressed in lung adenocarcinoma tissues. A high level of EphB4 protein expression was associated with lymph node metastasis in lung adenocarcinoma.
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BACKGROUND: Our study sought to investigate the therapeutic effects and mechanisms of miR-326-5p-overexpressing endothelial progenitor cells (EPCs) on acute myocardial infarction (AMI). METHODS: Mouse EPCs were isolated, purified, and identified by flow cytometry and uptake of DiI-ac-LDL. The target gene of miR-326-5p was predicted using target prediction algorithms and verified by dual-luciferase reporter assay, RT-qPCR, and Western blot. After EPCs were transfected with the agomir or antagomir of miR-326-5p, tube formation assay and Matrigel plug angiogenesis assay were conducted in four groups (NC, miR-326-5p agomir, miR-326-5p antagomir, and miR-326-5p agomir+Wnt1 agonist). In addition, a mouse model of MI was established and treated with the injection of miR-326-5p-EPCs, miR-326-5p-EPCs+ Wnt1 agonist, EPCs-NC, or PBS/control into the peri-infarcted myocardium. Subsequently, cardiac function was monitored by echocardiography at 7 and 28 days postoperatively. Finally, the infarcted hearts were collected at 28 days, and the size of myocardial infarction was measured by Masson's trichrome staining and the neovascularization in the peri-infarcted area was examined through immunofluorescence staining. RESULTS: Luciferase reporter assay indicated that Wnt1 was a direct target of miR-326-5p. Using RT-qPCR and Western blot analysis, we further demonstrated that the expression level of Wnt1 was negatively correlated with miR-326-5p expression in EPCs. Both in vitro study of tube formation assay and in vivo investigation of subcutaneous Matrigel plug assay revealed that the miR-326-5p agomir could significantly enhance the angiogenic capacity of EPCs, and this effect was partially inhibited by Wnt1 agonist. Meanwhile, miR-326-5p antagomir could obviously reduce the the angiogenic capacity of EPCs in vivo compared with that in the NC group. Moreover, the transplantation of miR-326-5p-overexpressing EPCs in the ischemic hearts of mice significantly enhanced the angiogenesis in the peri-infarcted zone and improved the cardiac function. However, the enhanced capacity of angiogenesis of miR-326-5p-overexpressing EPCs was remarkably neutralized by Wnt1 agonist, accompanied by the decreased improvement in cardiac function. CONCLUSION: miR-326-5p significantly enhanced the angiogenic capacity of EPCs. Transplantation of miR-326-5p-overexpressing EPCs improved cardiac function for AMI therapy, which can be a novel strategy for enhancing therapeutic angiogenesis in ischemic heart diseases.
Assuntos
Células Progenitoras Endoteliais/transplante , MicroRNAs/genética , MicroRNAs/uso terapêutico , Infarto do Miocárdio/terapia , Animais , Arteríolas/patologia , Sequência de Bases , Capilares/patologia , Feminino , Fibrose , Testes de Função Cardíaca , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Camundongos Endogâmicos C57BL , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Neovascularização Fisiológica , Proteína Wnt1/metabolismoRESUMO
BACKGROUND: Recently, various dynamically expressed lncRNAs are known to play critical roles in cancer progression. Small nucleolar RNA host genes (SNHG), a stable cytoplasmic lncRNA, which have been widely reported to act as an oncogene in non-small cell lung cancer (NSCLC). As an important member of SNHG, SNHG8 have been suggested to over-expressed in several cancer disease, while the biological function in NSCLC remains unclear. PURPOSE: Here we investigated the biological function and underlying mechanism of SNHG8 in human NSCLC. PATIENTS AND METHODS: The relationship between SNHG8 expression and clinicopathologic characteristic in NSCLC patients were observed from January 2014 to December 2014 in 120 NSCLC patients. The expression of SNHG8 were analyzed by qRT-PCR assay in cancer tissues and cells. Cell proliferation ability were detected in NSCLC cells by CCK-8 assay. Flow cytometric analysis were performed to detected the cell apoptosis and cell cycle. Luciferase assay and Western blot assay were performed on NSCLC cells to detected the underlying mechanism of SNHG8 in NSCLC. Moreover, Tumor xenografts in nude mice were performed to detected the in vivo function of SNHG8. RESULTS: SNHG8 was over-expressed in NSCLC tissues and cells. Patients with high SNHG8 expression have poorer overall survival (OS) and progression-free survival (PFS) than the patients with low SNHG8 expression. SNHG8 knockdown inhibited NSCLC cell proliferation in vitro and in vivo, arrested cell cycle in the G0/G1 phase via targeting miR-542-3p/CCND1/ CDK6, and induced cell apoptosis via activation of Caspase-3. CONCLUSION: SNHG8 negatively regulated miR-542-3p in NSCLC progression by regulating downstream effectors including CCND1 and CDK6. SNHG8 showed great potential for the application in the treatment of NSCLC.
RESUMO
Thyroid transcription factor-1 (TTF-1) is routinely used in the diagnosis of lung carcinoma and the subclassification of non-small cell lung cancer (NSCLC) in combination with other markers. The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are particularly effective in NSCLC patients harboring active EGFR mutations. EGFR protein is a poor prognostic factor for NSCLC patients. The relationship between TTF-1 expression and EGFR mutation and EGFR expression has not been well documented. The aim of this study was to investigate the relationship between TTF-1 and EGFR expression and mutation, and the clinical significance in lung adenocarcinoma. We analyzed TTF-1 expression, EGFR expression and mutation in 213 cases of lung adenocarcinoma. TTF-1 and EGFR expression levels were detected by immunohistochemical staining with monoclonal antibodies. EGFR mutations in exon 18, 19, 20 and 21 were assayed by the scorpion amplification refractory mutation system (ARMS) method. Forty-eight patients with EGFR mutations in exon 19 or 21 were detected from 91 patients with TTF-1 strong positive expression (3+) (52.74%), and 35 patients were detected with either exon 19 or 21 mutations from 54 patients with both TTF1 and EGFR positive expression (64.81%). Our data indicate that TTF-1 expression was positively related to EGFR mutation (P < 0.001) and EGFR expression (P < 0.001). EGFR expression level was positively related to its mutation (P = 0.003). These results indicate TTF-1 and EGFR positive lung adenocarcinomas frequently harbor EGFR mutations.