RESUMEN
Objective: This study investigated the impact of occupational mercury (Hg) exposure on human gene transcription and expression, and its potential biological mechanisms. Methods: Differentially expressed genes related to Hg exposure were identified and validated using gene expression microarray analysis and extended validation. Hg-exposed cell models and PTEN low-expression models were established in vitro using 293T cells. PTEN gene expression was assessed using qRT-PCR, and Western blotting was used to measure PTEN, AKT, and PI3K protein levels. IL-6 expression was determined by ELISA. Results: Combined findings from gene expression microarray analysis, bioinformatics, and population expansion validation indicated significant downregulation of the PTEN gene in the high-concentration Hg exposure group. In the Hg-exposed cell model (25 and 10 µmol/L), a significant decrease in PTEN expression was observed, accompanied by a significant increase in PI3K, AKT, and IL-6 expression. Similarly, a low-expression cell model demonstrated that PTEN gene knockdown led to a significant decrease in PTEN protein expression and a substantial increase in PI3K, AKT, and IL-6 levels. Conclusion: This is the first study to report that Hg exposure downregulates the PTEN gene, activates the PI3K/AKT regulatory pathway, and increases the expression of inflammatory factors, ultimately resulting in kidney inflammation.
Asunto(s)
Inflamación , Mercurio , Fosfohidrolasa PTEN , Humanos , Regulación hacia Abajo , Células HEK293 , Inflamación/inducido químicamente , Inflamación/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Interleucina-6/sangre , Mercurio/toxicidad , Exposición Profesional/efectos adversos , Fosfatidilinositol 3-Quinasas/metabolismo , Fosfatidilinositol 3-Quinasas/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Fosfohidrolasa PTEN/genética , Fosfohidrolasa PTEN/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
BACKGROUND: Hepatocellular carcinoma (HCC) is a common cancer and exhibits high morbidity and mortality in the world. We recently identified LHX3 as a preferentially expressed gene with a possible involvement in HCC. OBJECTIVE: To determine the expression, clinical relevance, prognostic significance and functions of LHX3 in HCC. MATERIALS AND METHODS: LHX3 expression was assessed in 190 cancerous and 40 adjacent non-cancerous tissues by PCR, western blot and immunohistochemistry. Associations between LHX3 expression and clinicopathological characteristics of patients were investigated. Correlations between LHX3 expression and overall survival of patients were analyzed by Kaplan-Meier and Cox-regression methods. Functional roles of LHX3 were evaluated by transwell assays. RESULTS: LHX3 expression is significantly increased in carcinoma tissues, and associated with clinical stage and metastasis of patients. LHX3 expression is much higher in the advanced-stage patients than the early-stage patients, and is sharply increased in metastasic patients. High LHX3 expression is associated with unfavorable overall survival, and is an independent prognostic factor of patients. Moreover, LHX3 is an unfavorable and independent prognostic factor unique to advanced-stage patients. Knockdown expression of LHX3 obviously inhibits tumor cell migration and invasion. CONCLUSION: LHX3 is an advanced-stage prognostic biomarker, and acts as a new potential metastatic oncogene in HCC.