Septin 9 hypermethylation contributes to migration and resistance to drug treatments in colon cancer

Purpose: To examine septin 9 gene-promoter methylation content in colorectal cancer and establish its significance in cancer progression and chemoresistance.Methods: Patient samples and colorectal cancer cell lines (CRC) were evaluated for septin 9 expression and promoter hypermethylation content. Septin 9 promoter methylation and expression in cells were perturbed by 5-AZA (5-aza-2'-deoxycytidine) treatments or overexpression and probed for changes in Rho A signaling, cell proliferation, and migration. Finally, the significance of septin 9 methylation in chemoresistance was probed using apoptotic assays in CRC cells and in a xenograft tumor model.Results: Expression analysis showed a reduction in septin 9 levels in tumor tissues (p < 0.001) and cell lines (p < 0.01), while an increase in septin 9 promoter methylation was seen, respectively ( > 2-fold; p < 0.01). Increasing septin 9 levels in CRC cells by 5-AZA treatments or overexpression showed decreased Rho A signaling and cell migration (p < 0.01), whereas cell proliferation remained unaffected. Furthermore, increasing septin 9 levels also exhibited increased cisplatin-induced apoptosis in CRC cells and reduced chemoresistance in the mouse (~2-fold; p < 0. 01).Conclusion: Septin 9 promoter hypermethylation reduces septin 9 expression and promotes migration and chemoresistance.Keywords: Septin 9, Hypermethylation, Colorectal cancer, Drug resistance, Rho A signalin

Knockdown of NOLC1 Inhibits PI3K-AKT Pathway to Improve the Poor Prognosis of Esophageal Carcinoma

Objective. Esophageal carcinoma (ESCA) is a common malignant gastrointestinal tumor. The abnormal expression of NOLC1 is involved in the tumorigenesis of various human tumors, whereas the function and mechanism of NOLC1 in ESCA remain unclear. In this study, we explored the relationship between NOLC1 and poor prognosis of ESCA, and its role and mechanism in the occurrence of ESCA. Methods. The NOLC1 expression in ESCA tissues and cell lines was determined by qRT-PCR, immunohistochemistry, or western blot. The Kaplan–Meier method was conducted to estimate the overall survival. Cox regression analysis was carried out to examine the association between patient characteristics and prognosis. A recombined lentiviral vector containing NOLC1 was applied for transfecting ESCA cells (Eca109 and TE-13) and established a stable cell line with low NOLC1 expression or high NOLC1 expression, in the absence or presence of PI3K inhibitor (LY294002) treatment. Cell proliferation, apoptosis rate, invasion ability, migration ability, and PI3K/AKT pathway were detected by CCK8 assay, flow cytometry, Transwell assay, wound-healing assay, and western blot. Results. NOLC1 overexpression was observed in ESCA tissues and ESCA cell lines (EC9706, Eca109, TE-13, Kyse170, T.TN) compared with adjacent normal tissues and normal esophageal cell line HEEC. NOLC1 overexpression was markedly associated with bigger tumor size, lymph node metastasis, and advanced TNM stage. Patients with NOLC1 overexpression have shorter overall survival than that of those with low NOLC1 expression. NOLC1 overexpression was considered to be an independent poor prognostic factor affecting overall survival. NOLC1 knockdown inhibited proliferation, migration, invasion, and cyclin B1 expression and promoted the apoptosis and cleaved-caspase-3 expression of Eca109 and TE-13 cells. NOLC1 overexpression accelerated proliferation, migration, invasion, and cyclin B1 expression and inhibited the apoptosis and cleaved-caspase-3 expression of ESCA cells via activating PI3K/AKT pathway. Rescue experiments showed that PI3K inhibitor (LY294002) could reverse the phenomenon caused by NOLC1 overexpression. Conclusion. NOLC1 may be a marker for poor prognosis. It can participate in the occurrence and development of ESCA via the PI3K/AKT pathway

Thermodynamic Calculation of Equilibrium Phases of K488 Alloy

The influence of equilibrium and alloy elements on the precipitation phases of K488 alloy was calculated and experimental analyzed by using Thermo-Calc thermodynamic calculation software. The results of calculation and experiment are shown that the alloy equilibrium phases are γ,γ',σ and carbides. In the alloy solidification process, Mo, Ti segregations are more serious. With the increase of C and Nb content, MC precipitation increased, but precipitation temperature decreased, the content of Ti is on the contrary. the increase of Al, Ti contents, γ' phase precipitations amount and precipitation temperature gradually increased. The content of Cr has most influence on the precipitation amount and precipitation temperature of the sigma phase. The calculation and experimental results have good consistency