CCNB1 and CCNB2 involvement in the pathogenesis of psoriasis: a bioinformatics study.

OBJECTIVE: The cell cycle-related proteins cyclin B1 (CCNB1) and cyclin B2 (CCNB2) are potentially involved in the underlying mechanisms of psoriasis. The present study aimed to explore this possibility using bioinformatics approaches. METHODS: CCNB1 and CCNB2 protein levels were evaluated in 14 psoriasis patients and five healthy controls by enzyme-linked immunosorbent assays, and their mRNA levels were evaluated using data from four publicly available datasets (GSE53552, GSE41664, GSE14905, and GSE13355). Comparison of high- and low-expressing groups were performed to reveal CCNB1- and CCNB2-related differentially expressed genes, which were then assessed based on gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses. Correlation analyses between CCNB1 and CCNB2 levels and immune infiltration, as well as typical targets of psoriasis, were also performed. RESULTS: Overall, 12 CCNB1 and CCNB2 common immune-related targets potentially involved in psoriasis were identified. These could regulate the cell cycle of through multiple pathways. In addition, CCNB1 and CCNB2 were found to potentially support the release of key molecular targets of psoriasis through the regulation of mast cell activation and macrophage polarization. CONCLUSIONS: These findings suggest that CCNB1 and CCNB2 may represent valuable molecular biomarkers of psoriasis, contributing to its onset and progression.

Mechanism of micro RNA-1182 overexpression in inhibiting malignant phenotype of glioma cells / 中华神经医学杂志

Objective:To investigate the micro RNA (miR)-1182 expression in glioma, and explore the regulation role and mechanism of miR-1182 overexpression in malignant phenotype of glioma cells.Methods:(1) The data of miR-1182 expressions of 198 glioma samples and survival of these glioma patients were downloaded from the official website of Chinese Glioma Genome Atlas(CGGA), and the differences of miR-1182 expression levels among glioma tissues of different pathologic types and different WHO grades were compared. Kaplan-Meier survival curve was used to analyze the relation between miR-1182 expression level and patient survival. (2) Human glioma cell lines A172, LN229, T98G, U87, and U251, and human normal astrocyte cell line NHA were routinely cultured in vitro, and the miR-1182 expression levels in each group were detected by real-time quantitative PCR (qPCR). (3) U87 and U251 cells were divided into miR-1182 transfection group and negative control group; the miR-1182 mimics and miR-1182 negative control sequence were transfected, respectively. After 48 h of transfection, 5-ethynyl-2'-deoxyuridine (EdU) staining was used to detect the cell proliferation ability, flow cytometry was used to detect the cell apoptosis, Transwell assay was used to detect the cell migration ability, and Western blotting was used to detect the expression levels of cyclin (C-myC, C-Jun, CCND1, and P21), phosphatidylinositol 3 kinase/protein kinase B (PI3K/Akt), and epithelial-mesenchymal transformation (EMT) pathway related proteins (N-cadherin, β-catenin, and vimentin). Results:(1) The miR-1182 expressions in glioma tissues of WHO grading III and IV were significantly lower as compared with those in glioma tissues of WHO grading II ( P<0.05). The median survival time in patients from the low miR-1182 expression group ([701.00±11.14] d) was significantly shorter than that in the high miR-1182 expression group ([1812.00±23.21] d, P<0.05). (2) As compared with that in NHA cell group, the miR-1182 expression levels in A172, LN229, T98G, U87 and U251 cell groups were significantly decreased ( P<0.05), and the decrease was most significant in U87 and U251 cell groups. (3) As compared with the negative control group, the U87 and U251 cells in miR-1182 transfection group had significantly weaker proliferation ability, significantly higher apoptosis rate, significantly decreased number of transmembrane cells, significantly decreased protein expression levels of C-MyC, C-Jun and CCND1, significantly increased P21 protein expression level, significantly decreased expression levels of PI3K, phosphorylated (p)-PI3K, Akt and p-Akt, and significantly decreased expression levels of N-cadherin, β-catenin and vimentin ( P<0.05). Conclusions:Glioma patients with low miR-1182 expression have poor prognosis. Low miR-1182 expression is noted in glioma cells. Overexpression of miR-1182 can inhibit the malignant phenotype of glioma cells, which may be related to cell cycle-related proteins, PI3K/Akt, and EMT pathway ralated proteins.

Analsis on the protective effect and mechanism of Nec-1 on cytotoxicity induced by cyclosporine A / 中国生化药物杂志

Objective To investigate the protective effect and its potential molecular mechanism of Nec-1 on cytotoxicity induced by cyclosporine A.Methods MRTEpiC, glomerular endothelial cell MGEC and mesangial cell line MMC were co-administered with Nec-1 and cyclosporin A in mouse renal tubular epithelial cell line, and then MTT assay and soft agar clone formation assay were used to detect Cell growth curve changes, clonal formation ability.Apoptosis was detected by flow cytometry.The expression of cyclin D1, CDK4, CDK2, Cyclin E and apoptosis-related Caspase 3 were detected by Western blot.Results After cyclosporine A action, the cell growth ability was significantly decreased and the clone formation ability was significantly decreased(P<0.05).Cyclin D1, CDK4, CDK2 and Cyclin E were significantly increased(P<0.05), but the ratio of apoptosis and the expression of Caspase 3 did not change.Nec-1 has obvious protective effect on cytotoxicity induced by cyclosporine A, which can increase the cell growth ability and clone formation ability, and reduce the cell cycle-related proteins Cyclin D1, CDK4, CDK2, Cyclin E.Conclusion Nec-1 has cytotoxic effect on the glomeruli and renal tubular cells by up-regulating the cell cycle-related proteins Cyclin D1, CDK4, CDK2 and Cyclin E, while Nec-1 has protective effect.

R-Phycoerythrin Induces SGC-7901 Apoptosis by Arresting Cell Cycle at S Phase.

R-Phycoerythrin (R-PE), one of the chemical constituents of red algae, could produce singlet oxygen upon excitation with the appropriate radiation and possibly be used in photodynamic therapy (PDT) for cancer. Documents reported that R-PE could inhibit cell proliferation in HepG2 and A549 cells, which was significative for cancer therapy. This is due to the fact that R-PE could kill cancer cells directly as well as by PDT. However, little is known about the cytotoxicity of R-PE to the SGC-7901 cell. In this study, it has been found that R-PE could inhibit SGC-7901 proliferation and induce cell apoptosis, which was achieved by arresting the SGC-7901 cell at S phase. CyclinA, CDK2 and CDC25A are proteins associated with the S phase, and it was found that R-PE could increase the expression of cyclin A protein and decrease the expression of CDK2 and CDC25A proteins. Thus, it was concluded that R-PE reduced the CDK2 protein activated through decreasing the CDC25A factor, which reduced the formation of Cyclin-CDK complex. The reduction of Cyclin-CDK complex made the SGC-7901 cells arrest at the S phase. Therefore, R-PE induced apoptosis by arresting the SGC-7901 cell at S phase was successful, which was achieved by the expression of the CDC25A protein, which reduced the CDK2 protein actived and the formation of Cyclin-CDK complex.

Expression of Proteins Related Cell Cycle and Apoptosis during Diethylnitrosamine (DEN)-induced Hepatocarcinogenesis in Rats

PURPOSE: To explore the role of cell cycle and apoptosis regulators during hepatocarcinogenesis, the expression of cell cycle-related proteins (cyclin D1 and p27kip1) and apoptosis-related proteins (p53, survivin, caspase 3). METHODS: Sprague-Dawley rats were given 120 ppm diethylnitrosamine (DEN) as a carcinogen and sequentially sacrificed. The expression of cell cycle and apoptotic related proteins were examined by light microscopy and immunohistochemistry. RESULTS: During the DEN-induced hepatocarcinogenesis, sequential histologic changes from preneoplastic lesions (altered hepatic cellular foci, hyperplastic nodules, and hepatocellular adenomas) and ultimately overt hepatocellular carcinomas and metastatic lesions were noted. The cyclin D1 were progressively increased from preneoplastic lesions to hepatocellular carcinomas. However, the p27kip1 and the survivine proteins did not show any other difference with the increasing degree of carcinogenesis. The p53 and caspase 3 proteins were more significantly increased in hepatocellular carcinomas than preneoplastic lesions. The cyclin D1 protein expression did not show any correlation with the expression of p27Kip1 protein, but the p53 expression was related to the expression of survivin and caspase 3. CONCLUSION: From the above results, over-expression of cyclin D1 plays a role in the early and late stages of hepatocarcinogenesis. In addition p53 and caspase 3 might be useful markers for evaluating the risk of malignant transformation.

Significance of Expression of p16, Cyclin D1, Rb, and p53 Protein and Correlation with Clinicopathologic Prognostic Factors in Invasive Ductal Carcinoma of the Breast

The retinoblastoma (Rb)/cyclin D1/p16 pathway is an important constituent of cell cycle regulation. Perturbations in this pathway due to a variety of genetic aberrations have been reported in many human cancers including breast cancer. We examined the significance of immunoexpression of p16 protein, cyclin D1 protein, Rb protein (pRb), and p53 protein in 128 cases of invasive breast carcinoma. The results were correlated with survival rate and clinicopathological variables, including age, histologic grade, lymph node status, tumor size, estrogen receptor (ER), and progesterone receptor (PR) content. Abnormal expressions of p16 and pRb which were defined as negative staining were seen in 21% and 43% of tumors, respectively. There was a significant inverse relationship between p16 and pRb expression. There was no correlation between p16 staining and any other parameters, including survival rate, cyclin D1, p53, and clinicopathologic variables. Surprisingly, there was a trend for tumors which were positive for pRb to be grade III ductal carcinomas. Cyclin D1 positivity was noted in 46% of cases. The expression of cyclin D1 protein was significantly higher in lower histologic grade, higher ER and PR expression. The expression of p53 protein showed a significant correlation with high tumor grade. In a Cox multivariate analysis, neither p16, pRb, cyclin D1 nor p53 was an independent predictor, but tumor size and lymph node status were independent predictors of patient outcome.