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[This retracts the article DOI: 10.3892/ol.2017.6433.].
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Hypoxia promotes the progression of hepatocellular carcinoma. However, the hypoxia regulatory network in hepatocellular carcinoma is known to be limited. Thus, this study aimed to identify the crucial hypoxia-associated genes and to explore their effects and molecular mechanisms in hepatocellular carcinoma cells. FUT11 was first identified as a crucial hypoxia-associated gene through bioinformatics analysis. High FUT11 mRNA levels were positively correlated with poor clinical parameters. FUT11 knockdown under normoxia and hypoxia both decreased hepatocellular carcinoma cell proliferation, colony formation, migration, and invasion. HIF1α binds to the promoter of FUT11 and increases its transcription and co-expression with FUT11 in hepatocellular carcinoma tissues. Overexpression of FUT11 in HIF1α knockdown cells reversed the inhibitory effects of HIF1α suppression on hepatocellular carcinoma cell proliferation and mobility under hypoxia. Therefore, our findings indicate that FUT11 is a key target gene of HIF1α, which can promote the proliferation and mobility of hepatocellular carcinoma cells. FUT11 may be a novel and effective target for blocking the hypoxia response of hepatocellular carcinoma cells.
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Carcinoma Hepatocelular/metabolismo , Fucosiltransferasas/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Carcinoma Hepatocelular/genética , Hipoxia de la Célula/genética , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Fucosiltransferasas/metabolismo , Expresión Génica/genética , Regulación Neoplásica de la Expresión Génica/genética , Células Hep G2 , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismoRESUMEN
Exosomal miRNAs are emerging as mediators of the interaction between mast cells (MCs) and tumor cells. The exosomal miRNAs can be internalized by liver cancer cells to inhibit cell metastasis. We explored the interaction between MCs and hepatocellular carcinoma (HCC) cells. We used hepatitis C virus E2 envelope glycoprotein (HCV-E2) to stimulate MCs and harvest MCs-derived exosomes to detect the miRNAs and changes of exosomal miRNAs before and after stimulation. Through miRNA microarray analysis, we identified 19 differentially expressed miRNAs in exosomes derived from MCs with or without HCV-E2 treatment. HCV-E2 not only increased the level of miRNA-490 in MCs and their secreted exosomes but also increased the levels of miRNA-490 in recipient HepG2 cells, which ultimately inhibited the ERK1/2 pathway. The transfection of antagomiR-490 significantly decreased the levels of miR-490 in MCs, MCs-derived exosomes, and recipient HepG2 cells and increased migration of HepG2, indicating that miR-490 is involved in the regulation of HepG2 cell migration. The present study suggests that MCs can inhibit HCC cell metastasis by inhibiting the ERK1/2 pathway by transferring the exosomal shuttle microRNAs into HCC cells, which provides new insights for the biological therapy of HCC induced by hepatitis C.
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OBJECTIVE: To study the clinical effect of combination of kurarinone (KR) and interferon a-lb (IFNalpha-1b) in treating chronic hepatitis B. METHODS: One hundred and forty-six patients with chronic hepatitis B were randomized into four groups. Under the basic conventional treatment, additional KR combined IFNa-lb was given to Group A, IFNa-lb to Group B and KR to Group C while none was given to Group D. The therapeutic course for them was 6 months and succeeded with 6 months of follow-up. Changes in liver histology, expression of transforming growth factor beta (TGF-beta) in liver tissue, and serum levels of TGF-beta, hyaluronic acid (HA), laminin (LN), collagen type IV (IVC), precollagen III (PCIII), as well as the negative conversion rate of HBeAg and HBV DNA, and normalization rate of alanine transaminase (ALT) before and after treatment were observed by immuno chemical method, RIA and ELISA. RESULTS: After treatment, in Group A, the scores of liver fibrosis and all the above-mentioned indexes significantly lowered, as compared with those in Group B and C, the difference was significant (P<0.05 or P<0.01). The negative conversion rate of TGF-beta in liver tissue was in accordance with the dynamic change of liver fibrosis. Comparison between Group B and C in those aspects showed insignificant difference (P >0.05). CONCLUSION: KR combined with IFNalpha-1b shows better effect in treating chronic hepatitis B than that of using either of the two alone.
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Flavonoides/uso terapéutico , Hepatitis B Crónica/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Fitoterapia , Adulto , ADN Viral/sangre , Quimioterapia Combinada , Medicamentos Herbarios Chinos/uso terapéutico , Femenino , Antígenos e de la Hepatitis B/sangre , Virus de la Hepatitis B/aislamiento & purificación , Humanos , Masculino , Persona de Mediana EdadRESUMEN
The triterpene profiles of different Ganoderma products was analysed by HPLC. The results showed that the seven-day fermented mycelia had little triterpene and different growth stages fruiting bodies almost had changeless triterpene. Compared with the fruiting body, the triterpene level of spore was lower. Among different Ganoderma species, Ganoderma atrum had little triterpenes too.