ABSTRACT
Aim To investigate the effect of T40 on malignant biological behavior of glioma U87 and U251 cells and its mechanism. Methods U87 and U251 cells were treated with T40 at different concentrations (0,1,2 and 4 p,mol • L"1). Changes of cell proliferation, clonal formation, apoptosis, migration and invasion in each group were detected by CCK-8, cloning plate, flow cytometry, scratch and transwell experi-ments. Bioinformatics was used to explore T40 targets and analyze the relationship between targets and glioma progression. The protein expression levels of PTPN1, PTPN2, Bcl-2, Bax, pro-caspase-3 , cleaved caspase- 3, MMP-2 and MMP-9 in each group were detected by Western blot. Results T40 significantly inhibited U87 and U251 proliferation, clone formation, migration and invasion and promoted apoptosis ( P < 0. 05 ) ; T40 had 37 targets, among which the expression levels of PTPN1 and PTPN2 were negatively correlated with the overall survival rate of glioma patients; T40 signifi cantly reduced the expression of PTPN1, PTPN2, Bcl- 2, MMP-2 and MMP-9 in U87 and U251 cells, and increased the expression of Bax and cleaved caspase-3 (P < 0. 05). Conclusions T40 inhibits the proliferation , migration and invasion of glioma U87 and U251 cells and promotes their apoptosis, and its mechanism may be related to the reduction of PTPN1 and PTPN2 expression.
ABSTRACT
Evaluar la posible asociación entre el SNP rs914458 (C>G) del gen PTPN1con la DM2 en una población de la zona urbana de Lima - Perú. Material y Métodos: El estudio incluyó un total de 216 personas de la zona urbana de Lima correspondientes a un grupo control (n = 123) y un grupo de pacientes diagnosticados con diabetes tipo 2 provenientes del Hospital A. Loayza (n = 93). La genotipificación del SNP se llevó a cabo mediante PCR y con un secuenciador ABI PRISM 310. El análisis de asociación se llevó a cabo con el uso de la herramienta web SNPStats para realizar cinco modelos de regresión logística. El efecto de la asociación genética se estableció con el valor de OR. Resultados: La frecuencia del MAF (alelo G) fue de 0.22 en el grupo de controles y en el grupo de pacientes. Ninguno de los modelos de regresión muestra valores de OR (considerando los CI) por encima o por debajo del valor de referencia. Conclusión: No se encontró asociación genética significativa entre el SNP rs914458 del gen PTPN1 y la DM2 para la población de la zona urbana de Lima - Perú...
Objective: Evaluate the association between SNP rs914458 (C>G) of PTPN1 gene with T2DM in a population from the urban area of Lima - Peru. Material and Methods: This study included a total of 216 subjects from the urban area of Lima. The number of subjects in control group was 123, and 93 patients diagnosed with type 2 diabetes from Hospital A. Loayza. SNP genotyping was performed by PCR and sequencing using ABI PRISM 310 DNA sequencer. The association analysis was carried out using the web tool SNPStats and five logistic regression models were performed. The effect of genetic association was established with the OR. Results: The frequency of MAF (allele G) was 0.22 in both control and patient groups. The OR values were not different from the reference values considering the respective confidence interval. Conclusion: No significant association was found between the SNP rs914458 and the PTPN1 gene with T2DM for the urban population of Lima - Peru...
Subject(s)
Humans , Genetic Association Studies , Gene Frequency , Protein Tyrosine Phosphatase, Non-Receptor Type 1 , PeruABSTRACT
Protein phosphorylation at tyrosine residues is a key regulatory event that modulates insulin signal transduction. We studied the PTPN1 gene with regard to susceptibility to Korean type 2 diabetes mellitus (T2DM) and its related quantitative traits. A total of seven SNPs [g.36171G>A (rs941798), g.58166G>A (rs3787343), g.58208A>G (rs2909270), g.64840C>T (rs754118), g.69560C>G (rs6020612), g.69866G>A (rs718050), and g.69934T>G (rs3787343)] were selected based on frequency (>0.05), linkage disequilibrium (LD) status, and haplotype tagging status. We studied the seven SNPs in 483 unrelated patients with type 2 diabetes (age: 64+/-2.8 years, onset age: 56+/-8.1 years; 206 men, 277 women) and 1138 nondiabetic control subjects (age: 64+/-2.9; 516 men, 622 women). The SNP rs941798 had protective effects against T2DM with an odds ratio of 0.726 (C.I. 0.541~0.975) and p-value=0.034, but none of the remaining six SNPs was associated with T2DM. Also, rs941798 was associated with blood pressure, HDL cholesterol, insulin sensitivity. rs941798 also has been associated with T2DM in previous reports of Caucasian-American and Hispanic-American populations. This is the first report that shows an association between PTPN1 and T2DM in the Korean as well as Asian population.