RESUMO
The miRNA processing genes play essential roles in the biosynthesis of mammalian miRNAs, and their genetic variants are involved in the development of various cancers. Our study aimed to determine the potential association between miRNA processing gene polymorphisms and cervical precancerous lesions. Five single nucleotide polymorphisms (SNPs), including Ran-GTP (RAN) rs14035, exportin-5 (XPO5) rs11077, DICER1 rs3742330, DICER1 rs13078, and TARBP2 rs784567, were genotyped in a case-control study to estimate risk factors of cervical precancerous lesions. The gene-environment interactions and haplotype association were estimated. We identified a 27% decreased risk of cervical precancerous lesions for individuals with minor G allele in DICER1 rs3742330 (odds ratio (OR) = 0.73, 95% confidence interval (95% CI) = 0.58-0.92, P = 0.009). The AG and AG/GG genotypes in DICER1 rs3742330 were also found to decrease the risk of cervical precancerous lesions (AG compared with AA: OR = 0.51, 95% CI = 0.35-0.73, P <0.001; AG/GG compared with AA: OR = 0.54, 95% CI = 0.39-0.77, P = 0.001). The GT haplotype in DICER1 had a risk effect on cervical precancerous lesions compared with the AT haplotype (OR = 1.36, 95% CI = 1.08-1.73, P = 0.010). A two-factor (DICER1 rs3742330 and human papillomavirus (HPV) infection) and two three-factor (model 1: rs3742330, passive smoking, and HPV infection; model 2: rs3742330, abortion history, and HPV infection) interaction models for cervical precancerous lesions were identified. In conclusion, the genetic variants in the miRNA processing genes and interactions with certain environmental factors might contribute to the risk of cervical precancerous lesions in southern Chinese women.
Assuntos
RNA Helicases DEAD-box/genética , Predisposição Genética para Doença , Infecções por Papillomavirus/genética , Ribonuclease III/genética , Neoplasias do Colo do Útero/genética , Adulto , China , Feminino , Estudos de Associação Genética , Genótipo , Haplótipos/genética , Humanos , Carioferinas/genética , MicroRNAs/genética , Pessoa de Meia-Idade , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/patologia , Polimorfismo de Nucleotídeo Único/genética , Lesões Pré-Cancerosas , Gravidez , Proteínas de Ligação a RNA/genética , Neoplasias do Colo do Útero/complicações , Neoplasias do Colo do Útero/patologia , Proteína ran de Ligação ao GTP/genéticaRESUMO
BACKGROUND: Acute T-lymphocyte leukaemia is a form of haematological malignancy with abnormal activation of NF-κB pathway, which results in high expression of A20 and ABIN1, which constitute a negative feedback mechanism for the regulation of NF-κB activation. Clinical studies have found that acute T-lymphocyte leukaemia patients are susceptible to Toxoplasma gondii infection; however, the effect of T. gondii on the proliferation and apoptosis of human leukaemia T-cells remains unclear. Here, we used the T. gondii ME-49 strain to infect human leukaemia T-cell lines Jurkat and Molt-4, to explore the effect of T. gondii on proliferation and apoptosis, which is mediated by NF-κB in human leukaemia T-cells. METHODS: The Tunel assay was used to detect cell apoptosis. Cell Counting Kit-8 was used to detect cell proliferation viability. The apoptosis level and the expression level of NF-κB related proteins in human leukaemia T-cells were detected by flow cytometry and Western blotting. RESULTS: Western blotting analyses revealed that the T. gondii ME-49 strain increased the expression of A20 and decreased both ABIN1 expression and NF-κB p65 phosphorylation. By constructing a lentiviral-mediated shRNA to knockdown the A20 gene in Jurkat T-cells and Molt-4 T-cells, the apoptosis levels of the two cell lines decreased after T. gondii ME-49 infection, and levels of NF-κB p65 phosphorylation and ABIN1 were higher than in the non-konckdown group. After knockingdown ABIN1 gene expression by constructing the lentiviral-mediated shRNA and transfecting the recombinant expression plasmid containing the ABIN1 gene into two cell lines, apoptosis levels and cleaved caspase-8 expression increased or decreased in response to T. gondii ME-49 infection, respectively. CONCLUSIONS: Our data suggest that ABIN1 protects human leukaemia T-cells by allowing them to resist the apoptosis induced by T. gondii ME-49 and that the T. gondii ME-49 strain induces the apoptosis of human leukaemia T-cells via A20-mediated downregulation of ABIN1 expression.
Assuntos
Apoptose , NF-kappa B/metabolismo , Linfócitos T/patologia , Toxoplasma/genética , Proteína 3 Induzida por Fator de Necrose Tumoral alfa/genética , Proliferação de Células , Sobrevivência Celular , Proteínas de Ligação a DNA/genética , Regulação para Baixo , Regulação da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Células Jurkat , Fosforilação , Transdução de Sinais/genética , Proteína 3 Induzida por Fator de Necrose Tumoral alfa/deficiência , Regulação para CimaRESUMO
Background: Lipoma preferred partner (LPP) and T-cell activation Rho GTPase activating protein (TAGAP) polymorphisms might influence the susceptibility to celiac disease. Therefore, we performed a meta-analysis by identifying relevant studies to estimate the risks of these polymorphisms on celiac disease. Methods: The PubMed, Web of Science and Embase databases were searched (up to October 2016) for LPP rs1464510 and TAGAP rs1738074 polymorphisms. Results: This meta-analysis included the same 7 studies for LPP rs1464510 and TAGAP rs1738074. The minor risk A allele at both rs1464510 and rs1738074 carried risks (odds ratios) of 1.26 (95% CI: 1.22-1.30) and 1.17 (95% CI: 1.14-1.21), respectively, which contributed to increased risks in all celiac disease patients by 10.72% and 6.59%, respectively. The estimated lambdas were 0.512 and 0.496, respectively, suggesting that a co-dominant model would be suitable for both gene effects. Conclusions: This meta-analysis provides robust estimates that polymorphisms in LPP and TAGAP genes are potential risk factors for celiac disease in European and American. Prospective studies and more genome-wide association studies (GWAS) are needed to confirm these findings, and some corresponding molecular biology experiments should be carried out to clarify the pathogenic mechanisms of celiac disease.
Assuntos
Doença Celíaca/genética , Proteínas do Citoesqueleto/genética , Proteínas Ativadoras de GTPase/genética , Predisposição Genética para Doença/genética , Proteínas com Domínio LIM/genética , Polimorfismo de Nucleotídeo Único , Alelos , HumanosRESUMO
Shiyan district in Hubei province is a famous locality of high-quality turquoise with brightcolor, finegrain in the world. Erlitou archacologicalsite, which is about 300km north to the Shiyan Turquoise mine, has been excavated a remarkable number of turquoise artifacts since 2002. Some researchers infer that there was "a road of turquoise" between the two sites in history. In order to check the inference, and identify local features of the turquoises found in Shiyan, and Eelitou site as well, spectra of three turquoise groups from Shiyan, Hubei and one group of Erlitou unearthed samples were obtained by means of IR. Their spectra have visible differences in the 1 200-950 and 700-400 cm(-1) range. Peak 1 174 cm(-1) appears only in samples from Wenfeng, and from 700 to 400 cm(-1), 5 peaks show in samples from Wenfeng while 7 peaks emerge from the other two sites. Turquoises in Erlitou site have similar spectra to those from Qingu and Yungaisi, and are more similar to Yungaisi of peak around 1 159 cm(-1). According to A = lg(1/T) , intensity of transmittance spectra were calculated and then Ratios(A783 cm(-1)/A837 cm(-1)) were yielded. The ratios of samples from Qingu, Wenfeng, Yungaisi and Erlitou site are 0.819-0.920, 0.870-1.010, 0.806-0.860 and 0.827-0.878 respectively, allowing for a suggestion that turquoise in Erlitou site was the most probable from Yungaisi. This research can be used as example for identifying origin of the unearthed turquoise relics, which is more likely a good tool for archeological research.
