RESUMO
Background: Estrogen-related receptor-α (ESRRA) is an orphan nuclear receptor, expressing at high level in exuberant metabolism organs and acting as transcription factor. High expression was found in many malignances but no research was done in gastric cancer (GC), where lipid metabolism disorder is common. Methods: Kaplan-Meier plot was utilized to find the relationship between ESRRA expression and patients' prognoses. The expression level of ESRRA was measured by real-time PCR. The protein expression levels were tested with western-blot and immunohistochemistry. Cell cycle and apoptosis was identified with flow cytometry. RNA-seq, bioinformatics analysis, dual-luciferase assay and ChIP assay were used to predict and validate ESRRA's target gene and binding motif. Animal models were also introduced in our study. Results: ESRRA expression is notably higher in GC cell lines and high ESRRA levels are correlated to poor prognoses. ESRRA silencing decreased GC cell viability, migration, and invasion capacities. Its downstream gene DSN1 was spotted by RNA-seq and confirmed by later bioinformatics analyses, dual-luciferase, and ChIP assays. Western-blot showed G2M arrest caused by ESRRA silencing was via CDC25C-CDK1-Cyclin B1 pathway. Conclusion: ESRRA/DSN1/CDC25C-CDK1-Cyclin B1 is of great importance in GC development. ESRRA could be a potential target as well as prognostic marker in GC.
Assuntos
Proteína Quinase CDC2/metabolismo , Proteínas Cromossômicas não Histona/metabolismo , Ciclina B1/metabolismo , Receptores de Estrogênio , Neoplasias Gástricas , Fosfatases cdc25/metabolismo , Animais , Apoptose , Biomarcadores Tumorais , Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular , Descoberta de Drogas , Regulação Neoplásica da Expressão Gênica , Humanos , Metabolismo dos Lipídeos , Prognóstico , Receptores de Estrogênio/genética , Receptores de Estrogênio/metabolismo , Transdução de Sinais , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Receptor ERRalfa Relacionado ao EstrogênioRESUMO
To improve the effect of coal fly ash on the remediation of heavy metal polluted soils, the active silicate material (ASM) was prepared by coal fly ash and the remediation of lead polluted soils by ASM was investigated in this study. To study the reaction mechanism between ASM and Pb(II) in soil, the Pb(II) adsorption by ASM was investigated by a series of batch experiments. The result shows that the maximum adsorption capacity of ASM was 300.62 mg g-1 according to the Langmuir isotherm model. The average adsorption energy obtained from the D-K model revealed that the adsorption process of ASM is the ion-exchange process. To apply the ASM to the remediation of lead polluted soils, the soil stabilization experiment and pot experiment were carried out. The results reveal that ASM can reduce the mobility and bioavailability of lead in the soils by transforming the lead from exchangeable fraction, carbonate fraction and reducible fraction to oxidizable fraction and residual fraction. Moreover, ASM can improve the growth of pakchoi by promoting the production of chlorophyll. Furthermore, ASM can reduce the Pb accumulation of pakchoi by inhibiting the absorption of lead in the roots. It is anticipated that this study can provide a novel active silicate material for the application of coal fly ash in heavy metal pollution treatment.