RESUMO
BACKGROUND: Hepatocellular carcinoma (HCC) is still a major health burden in China considering its high incidence and mortality. Long non-coding RNAs (lncRNAs) were found playing vital roles in tumor progression, suggesting a new way of diagnosis and prognosis prediction, or treatment of HCC. This study was designed to investigate the role of HIF1A-AS1 during the progression of HCC and to explore its related mechanisms. METHODS: The expression of HIF1A-AS1 was detected in 50 paired carcinoma tissues and adjacent normal tissues by quantitative real-time PCR assay. HCC cell apoptosis was induced by nutrient-deficient culture medium and detected by Cell Counting Kit-8 and flow cytometer assays. HIF1A-AS1 inhibition in HCC cells was accomplished by small interfering RNA transfection. RESULTS: HIF1A-AS1 was overexpressed in HCC tissues and was associated with tumor size, TNM stage, and lymph node metastasis. Compared with the low HIF1A-AS1 group, the high HIF1A-AS1 group had a shorter overall survival and a worse disease-free survival. HIF1A-AS1 expression was significantly higher in HCC cell lines (7721 and Huh7) than that in normal hepatocyte cell line L02 under normal culture condition. However, under nutrient-deficient condition, HIF1A-AS1 expression was significantly increased in both HCC and normal hepatocyte cell lines and was increased with the prolongation of nutrient-free culture. Inhibition of HIF1A-AS1 promoted starvation-induced HCC cell apoptosis. Furthermore, inhibition of HIF1A-AS1 could also reduce starvation-induced HCC cell autophagy. The expression of HIF-1α and phosphorylated mTOR was significantly decreased in HCC cells after HIF1A-AS1 inhibition. CONCLUSIONS: HIF1A-AS1, overexpressed in HCC and associated with HCC prognosis, could regulate starvation-induced HCC cell apoptosis by reducing HIF-1α/mTOR-mediated autophagy, promoting HCC cell progression.
Assuntos
Apoptose/genética , Autofagia/genética , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , RNA Longo não Codificante/metabolismo , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Técnicas de Cultura de Células/métodos , Hipóxia Celular , Linhagem Celular Tumoral , Meios de Cultura/metabolismo , Progressão da Doença , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Hepatectomia , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Fígado/patologia , Fígado/cirurgia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Nutrientes/metabolismo , Prognóstico , RNA Longo não Codificante/genética , RNA Interferente Pequeno/metabolismo , Transdução de Sinais/genética , Serina-Treonina Quinases TOR/metabolismoRESUMO
Acidithiobacillus ferrooxidans (A. ferrooxidans) was applied in coal biodesulfurization and coal's pyrite bioleaching. The result showed that A. ferrooxidans had significantly promoted the biodesulfurization of coal and bioleaching of coal's pyrite. After 16 days of processing, the total sulfur removal rate of coal was 50.6%, and among them the removal of pyritic sulfur was up to 69.9%. On the contrary, after 12 days of processing, the coal's pyrite bioleaching rate was 72.0%. SEM micrographs showed that the major pyrite forms in coal were massive and veinlets. It seems that the bacteria took priority to remove the massive pyrite. The sulfur relative contents analysis from XANES showed that the elemental sulfur (28.32%) and jarosite (18.99%) were accumulated in the biotreated residual coal. However, XRD and XANES spectra of residual pyrite indicated that the sulfur components were mainly composed of pyrite (49.34%) and elemental sulfur (50.72%) but no other sulfur contents were detected. Based on the present results, we speculated that the pyrite forms in coal might affect sulfur biooxidation process.