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PURPOSE: The activation of cGAS-STING pathway can be triggered by cytosolic double-stranded DNA (dsDNA) in tumor and non-tumor compartments. We aim to assess the constitutive expression of dsDNA-cGAS-STING axis in different cellular contexts and compare their relative contribution to clinical outcomes. METHODS: A cohort of 154 cases of patients with newly diagnosed gastric cancer were enrolled in this study to evaluate the histo-score of cytosolic dsDNA, cGAS, and STING via immunohistochemistry as well as the types and densities of tumor-infiltrating immune cells. Kaplan-Meier method, multivariable regression, and receiver operating characteristic curve were implemented to analyze the prognostic efficacy of dsDNA-cGAS-STING axis in distinct compartments. RESULTS: The supra-normal concentration of cytosolic dsDNA correlated with the constitutive expression of cGAS-STING pathway in tumor compartments. In contrast to the lack of STING within cancer cells, the higher STING expression in non-tumor compartments indicated a transcellular cGAS-STING activation. Cancer cell-extrinsic STING was supported to potentiate nucleic acid immunity by sensing tumor-derived dsDNA fragments. Compartmental analyses also confirmed that the level of STING expressed in non-tumor cells was associated with the infiltration of protective immune cells, leading to the prolonged overall survival. Multivariate analysis further identified the independent prognostic value of cancer cell-extrinsic STING and its predictive accuracy could be significantly improved in combination with the immune cell infiltration. CONCLUSIONS: Cancer cell-extrinsic STING facilitates the remodeling of immune-active tumor microenvironment and acts as an independent prognostic factor in gastric cancer.
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Pituitary adenoma is one of the most common tumors in the neuroendocrine system. This study investigated the effects of long non-coding RNAs (lncRNAs) highly up-regulated in liver cancer (HULC) on rat secreting pituitary adenoma GH3 cell viability, migration, invasion, apoptosis, and hormone secretion, as well as the underlying potential mechanisms. Cell transfection and qRT-PCR were used to change and measure the expression levels of HULC, miR-130b, and FOXM1. Cell viability, migration, invasion, and apoptosis were assessed using trypan blue staining assay, MTT assay, two-chamber transwell assay, Guava Nexin assay, and western blotting. The concentrations of prolactin (PRL) and growth hormone (GH) in culture supernatant of GH3 cells were assessed using ELISA. The targeting relationship between miR-130b and FOXM1 was verified using dual luciferase activity. Finally, the expression levels of key factors involved in PI3K/AKT/mTOR and JAK1/STAT3 pathways were evaluated using western blotting. We found that HULC was highly expressed in GH3 cells. Overexpression of HULC promoted GH3 cell viability, migration, invasion, PRL and GH secretion, as well as activated PI3K/AKT/mTOR and JAK1/STAT3 pathways. Knockdown of HULC had opposite effects and induced cell apoptosis. HULC negatively regulated the expression of miR-130b, and miR-130b participated in the effects of HULC on GH3 cells. FOXM1 was a target gene of miR-130b, which was involved in the regulation of GH3 cell viability, migration, invasion, and apoptosis, as well as PI3K/AKT/mTOR and JAK1/STAT3 pathways. In conclusion, HULC tumor-promoting roles in secreting pituitary adenoma might be via down-regulating miR-130b, up-regulating FOXM1, and activating PI3K/AKT/mTOR and JAK1/STAT3 pathways.
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Adenoma/patología , Neoplasias Hipofisarias/patología , ARN Largo no Codificante/fisiología , Adenoma/genética , Adenoma/metabolismo , Animales , Apoptosis/fisiología , Western Blotting , Línea Celular Tumoral , Ensayos de Migración Celular , Movimiento Celular/fisiología , Supervivencia Celular/fisiología , Ensayo de Inmunoadsorción Enzimática , Proteína Forkhead Box M1/análisis , Proteína Forkhead Box M1/metabolismo , Humanos , Janus Quinasa 1/análisis , Janus Quinasa 1/metabolismo , Luciferasas , MicroARNs/análisis , MicroARNs/metabolismo , Fosfatidilinositol 3-Quinasas/análisis , Fosfatidilinositol 3-Quinasas/metabolismo , Neoplasias Hipofisarias/genética , Neoplasias Hipofisarias/metabolismo , Proteínas Proto-Oncogénicas c-akt/análisis , Proteínas Proto-Oncogénicas c-akt/metabolismo , ARN Largo no Codificante/análisis , Ratas , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factor de Transcripción STAT3/análisis , Factor de Transcripción STAT3/metabolismo , Serina-Treonina Quinasas TOR/análisis , Serina-Treonina Quinasas TOR/metabolismo , TransfecciónRESUMEN
Pituitary adenoma is one of the most common tumors in the neuroendocrine system. This study investigated the effects of long non-coding RNAs (lncRNAs) highly up-regulated in liver cancer (HULC) on rat secreting pituitary adenoma GH3 cell viability, migration, invasion, apoptosis, and hormone secretion, as well as the underlying potential mechanisms. Cell transfection and qRT-PCR were used to change and measure the expression levels of HULC, miR-130b, and FOXM1. Cell viability, migration, invasion, and apoptosis were assessed using trypan blue staining assay, MTT assay, two-chamber transwell assay, Guava Nexin assay, and western blotting. The concentrations of prolactin (PRL) and growth hormone (GH) in culture supernatant of GH3 cells were assessed using ELISA. The targeting relationship between miR-130b and FOXM1 was verified using dual luciferase activity. Finally, the expression levels of key factors involved in PI3K/AKT/mTOR and JAK1/STAT3 pathways were evaluated using western blotting. We found that HULC was highly expressed in GH3 cells. Overexpression of HULC promoted GH3 cell viability, migration, invasion, PRL and GH secretion, as well as activated PI3K/AKT/mTOR and JAK1/STAT3 pathways. Knockdown of HULC had opposite effects and induced cell apoptosis. HULC negatively regulated the expression of miR-130b, and miR-130b participated in the effects of HULC on GH3 cells. FOXM1 was a target gene of miR-130b, which was involved in the regulation of GH3 cell viability, migration, invasion, and apoptosis, as well as PI3K/AKT/mTOR and JAK1/STAT3 pathways. In conclusion, HULC tumor-promoting roles in secreting pituitary adenoma might be via down-regulating miR-130b, up-regulating FOXM1, and activating PI3K/AKT/mTOR and JAK1/STAT3 pathways.
Asunto(s)
Humanos , Animales , Ratas , Neoplasias Hipofisarias/patología , Adenoma/patología , ARN Largo no Codificante/fisiología , Ensayo de Inmunoadsorción Enzimática , Transfección , Adenoma/genética , Adenoma/metabolismo , Movimiento Celular/fisiología , Supervivencia Celular/fisiología , Western Blotting , Apoptosis/fisiología , MicroARNs/análisis , Línea Celular Tumoral , Factor de Transcripción STAT3/análisis , Janus Quinasa 1/análisis , Janus Quinasa 1/metabolismo , Ensayos de Migración Celular , Proteína Forkhead Box M1/análisis , Proteína Forkhead Box M1/metabolismo , LuciferasasRESUMEN
OBJECTIVE: The aim of this study was to analyze the associations between occupational stress, burnout and turnover intention and explore their associated factors among managerial staff in Guangzhou, China. METHODS: This cross-sectional study recruited 288 managerial employees from a Sino-Japanese joint venture automobile manufacturing enterprise in Guangzhou. The questionnaire included questions about sociodemographic characteristics, smoking, drinking and physical activity and the Chinese versio ns of the Occupational Stress Indicator (OSI), Maslach Burnout Inventory (MBI), Eysenck Personality Questionnaire (EPQ), Simplified Coping Style Questionnaire (SCSQ) and Social Support Rating Scale (SSRS). The response rate was 57.6%. Stepwise regression analysis was performed to examine the associations between burnout and occupational stress and turnover intention and related factors. RESULTS: The respondents had a high level burnout on the personal accomplishment subscale and had a high prevalence of turnover intention. Neuroticism, psychoticism, job satisfaction, occupational stress and social support were strong predictors of emotional exhaustion. Psychoticism, passive coping, occupational stress, objective support, utilization of support, male gender and job satisfaction were strong predictors of depersonalization. Active and passive coping and job satisfaction were strong predictors of personal accomplishment. Job dissatisfaction and emotional exhaustion were strong predictors of turnover intention. CONCLUSIONS: High occupational stress and low job satisfaction were associated with high burnout, particularly in the emotional exhaustion and depersonalization dimensions. Low job satisfaction and high emotional exhaustion were associated with high turnover intention among employees. Personality traits, social support and coping style were also found to be associated with burnout.