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1.
Acta Pharmacol Sin ; 36(10): 1237-45, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25937637

RESUMO

AIM: Argonaute2 (AGO2) protein is the active part of RNA-induced silencing complex, cleaving the target mRNA strand complementary to their bound siRNA. An increasing number of miRNAs has been identified as essential to angiogenesis of hepatocellular carcinoma (HCC). In this study we investigated how AGO2 affected HCC angiogenesis. METHODS: Human HCC cell lines HepG2, Hep3B, Huh7, SMMC-7721, Bel-7404, MHCC97-H and LM-3, and human umbilical vein endothelial cells (HUVEC) were tested. The expression of AGO2 in HCC cells was knocked down with siRNA and restored using recombinant adenovirus expressing Ago2. The levels of relevant mRNAs and proteins were examined using RT-PCR, Western blot and EILSA. Nude mice were implanted with Huh7 or SMMC-7721 cells, and tumor volumes were measured. After the mice were euthanized, the xenograft tumors were used for immunohistological analysis. RESULTS: In 6 HCC cell lines, AGO2 protein expression was significantly correlated with VEGF expression (r=+0.79), and with VEGF secretion (r=+0.852). Knockdown of Ago2 in Huh7 cells and SMMC-7721 cells substantially decreased VEGF expression, whereas the restoration of AGO2 reversed both VEGF expression and secretion. Furthermore, knockdown of Ago2 significantly up-regulated the expression of PTEN (a tumor suppressor involved in the inhibition of HCC angiogenesis), and vice versa. Moreover, the specific PTEN inhibitor bisperoxovanadate (7, 14, 28 nmol/L) dose-dependently restored the expression of VEGF and the capacity of HCC cells to induce HUVECs to form capillary tubule structures. In the xenograft nude mice, knockdown of Ago2 markedly suppressed the tumor growth and decreased PTEN expression and CD31-positive microvascular in the xenograft tumors. CONCLUSION: A direct relationship exists between the miRNA processing machinery AGO2 and HCC angiogenesis that is mediated by the AGO2/PTEN/VEGF signaling pathway. The results suggest the high value of Ago2 knockdown in anti-angiogenesis therapy for HCC.


Assuntos
Proteínas Argonautas/genética , Carcinoma Hepatocelular/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/genética , Neovascularização Patológica/genética , PTEN Fosfo-Hidrolase/genética , Fator A de Crescimento do Endotélio Vascular/genética , Animais , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/terapia , Linhagem Celular Tumoral , Células Hep G2 , Células Endoteliais da Veia Umbilical Humana , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Camundongos Nus , MicroRNAs/genética , Neovascularização Patológica/patologia , Neovascularização Patológica/terapia , RNA Interferente Pequeno/genética , Terapêutica com RNAi , Transdução de Sinais
2.
Ying Yong Sheng Tai Xue Bao ; 26(11): 3503-8, 2015 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-26915209

RESUMO

To explore the adaptability of plant under salt stress to crude oil pollution of soil and improvement measures, a pot experiment of Helianthus annuus seedlings was conducted using orthogonal experiment method with crude oil-sodium chloride-desulfurization gypsum and cinder-zeolite-desulfurization gypsum-sawdust. The results showed that, with the increase of soil crude oil concentration, the relative growth rate (RGR) of plant height, RGR of aboveground biomass and root N: P ratios of H. annuus seedlings decreased significantly, while the activity of SOD and CAT increased at first and then decreased significantly. The RGR of plant height and aboveground biomass significantly increased (P < 0.05), while the activity of SOD decreased gradually with the increase of the volume fraction of sawdust, indicating that sawdust had the most significant effect in comparison with cinder, zeolite, desulfurization gypsum under salinization condition. The crude oil pollution of soil could decrease the relative growth rate of H. annuus seedling, and sawdust could reduce the influence of crude oil pollution on plant growth under salt stress.


Assuntos
Adaptação Fisiológica , Helianthus/fisiologia , Poluição por Petróleo , Salinidade , Poluentes do Solo , Biomassa , Sulfato de Cálcio , Helianthus/efeitos dos fármacos , Raízes de Plantas/crescimento & desenvolvimento , Plântula/crescimento & desenvolvimento , Solo/química , Estresse Fisiológico
3.
World J Gastroenterol ; 18(31): 4207-14, 2012 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-22919255

RESUMO

AIM: To perform a systematic meta-analysis to investigate the association between X-ray repair cross-complementing group 1 (XRCC1) polymorphisms and hepatocellular carcinoma (HCC) risk. METHODS: Relevant studies extracted from PubMed, Embase, Wanfang, VIP and the Chinese National Knowledge Infrastructure databases up to March 2012 were included in the study. Stata software, version 11.0, was used for the statistical analysis. The odds ratios (ORs) and 95% confidence interval (CI) of the XRCC1 polymorphisms in HCC patients were analyzed and compared with healthy controls. The meta-analysis was performed using fixed-effect or random-effect methods, depending on the absence or presence of significant heterogeneity. RESULTS: Eleven studies with 2075 HCC cases and 2604 controls met our eligibility criteria (four studies, 888 cases and 938 controls for Arg194Trp, four studies, 858 cases and 880 controls for Arg280His, and nine studies, 1845 cases and 2401 controls for Arg399Gln). The meta-analysis revealed no associations between the Arg194Trp and Arg399Gln polymorphisms of the XRCC1 gene and HCC risk under all contrast models (codominant, dominant and recessive models) in the overall analysis and sensitivity analysis (the studies with controls not in the Hardy-Weinberg equilibrium were excluded). For XRCC1 Arg280His polymorphism, the overall analysis revealed the significant association between the His/His genotype and the increased risk of HCC (His/His vs Arg/Arg model, OR: 1.96, 95% CI: 1.03-3.75, P = 0.04). However, sensitivity analysis showed an altered pattern of result and non-significant association (OR: 2.06, 95% CI: 0.67-6.25, P = 0.20). The heterogeneity hypothesis test did not reveal any heterogeneity, and Begg's and Egger's tests did not find any obvious publication bias. CONCLUSION: The XRCC1 Arg194Trp and Arg399Gln polymorphisms are not associated with HCC risk. More rigorous association studies are needed to verify the involvement of XRCC1 Arg280His polymorphism in HCC susceptibility.


Assuntos
Carcinoma Hepatocelular/genética , Proteínas de Ligação a DNA/genética , Neoplasias Hepáticas/genética , Polimorfismo Genético/genética , Estudos de Casos e Controles , Predisposição Genética para Doença/genética , Genótipo , Humanos , Viés de Publicação , Fatores de Risco , Proteína 1 Complementadora Cruzada de Reparo de Raio-X
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