Silencing of TGIF attenuates the tumorigenicity of A549 cells in vitro and in vivo.

The aim of this study was to investigate the effects of the silencing of the TG-interacting factor (TGIF) on the tumorigenicity of A549 cells in vitro and in vivo. Stable TGIF-silenced A549 cells were established by infecting shRNA lentiviral particles. Western blotting analysis was used to detect the expression of proteins. Cell cycle was detected by flow cytometry. Soft agar assay and tumor formation assay in nude mice were applied. The silencing of TGIF inhibited A549 cell proliferation, colony formation in vitro, growth of tumor xenograft in vivo, and arrested the cell cycle in the G1 phase. The expression of CDK4, cyclin D1, and phospho-Rb was markedly decreased in the A549-shTGIF cells compared with the A549-shcon cells, and p21 was markedly increased in the A549-shTGIF cells compared with the A549-shcon cells. A lower level of ß-Catenin protein expression was observed in the A549-shTGIF cells than that in the A549-shcon cells. The silencing of TGIF attenuates the tumorigenicity of A549 cells in vitro and in vivo.

Elevated expression of TGIF is involved in lung carcinogenesis.

The purpose of this study was to explore the expression of TG-interacting factor (TGIF) in lung carcinogenesis. Malignant transformation of human bronchial epithelial (16HBE) cell was established by benzo(a)pyrene (BaP) treatment. Soft agar assay and tumor formation assay in nude mice were applied. Tumorigenesis experiment in vivo was done by BaP treatment. Western blotting, immunohistochemistry, and quantitative polymerase chain reaction were used to detect TGIF expression. We observed a higher level of TGIF messenger RNA (mRNA) in lung cancer tissues than that in paracancerous tissues. We observed significantly higher levels of TGIF mRNA and protein in A549 and H1299 cell lines than that in 16HBE cell. Increased expressions of TGIF protein and mRNA were observed in 16HBE cells induced by BaP treatment as compared to those in solvent control group. We observed significantly higher levels of TGIF mRNA and protein in 16HBE-BaP cells than that in 16HBE-control cells. We observed significantly higher levels of TGIF mRNA and protein in mice lung tissues treated with BaP than that in control group. Our results suggested that elevated expression of TGIF was involved in lung carcinogenesis.

Benzo(a)pyrene promotes A549 cell migration and invasion through up-regulating Twist.

Benzo(a)pyrene (BaP) is one of the strongest carcinogens in cigarette smoke, which is an established human carcinogen. Twist, a transcription factor of the basic helix-loop-helix class, is reported to regulate lung cancer metastasis. Evidence has shown that BaP could induce Twist mRNA expression in non-small cell lung cancer (NSCLC) cell line A549 and promote lung adenocarcinoma cell invasion. However, it is unclear whether BaP promotes the migration and invasion of NSCLC cells by Twist modulation. A549 cell was exposed to BaP for different time. MTT assay was applied to assess cell proliferation. Silencing of Twist was done by small interfering RNA. Wound-healing assay was used to evaluate the capability of cell migration. Transwell assay was used to detect the capability of cell invasion. Western blotting and quantitative polymerase chain reaction were used to detect Twist expression. The levels of Twist protein expression and mRNA expression were increased with the treatment of BaP, compared with solvent control. The capability of wound healing of A549 cells was increased in BaP-treated group, compared with solvent control. BaP enhanced the capability of invasion of A549 cells. Twist knockdown could block the migration and invasion of A549 cells induced by BaP treatment. The mRNA levels of Twist were higher in metastatic NSCLC tissue samples than in primary NSCLC tissue samples, and higher levels of Twist mRNA were observed in metastatic NSCLC tissue samples with smoking history than in those with nonsmoking history. BaP treatment could promote the migration and invasion of NSCLC cells by up-regulating Twist expression.

E-cadherin (CDH1) gene promoter polymorphism and the risk of colorectal cancer : a meta-analysis.

OBJECTIVE: Published data on the relationship between E-cadherin (CDH1) gene promoter polymorphisms and colorectal cancer (CRC) risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was carried out. METHODS: In this meta-analysis, we evaluated reported studies of associations between polymorphisms of CDH1 gene promoter -160 C > A and -347 G > GA site, and CRC risk using fixed-effects model and random-effects model. RESULTS: We found decreased CRC risk among subjects carrying CDH1 -160AA (odds ratio [OR] = 0.86, 95 percent confidence interval [95% CI]: 0.75-0.98) and CA + AA (OR = 0.92, 95% CI: 0.87-0.98), using 4,652/4,428 cases/controls and 7,866/7,689 cases/controls from ten studies, respectively. We found a protective effect of the CDH1 -160CA + AA polymorphisms for CRC in distal site tumor population and population-based control in stratified analysis. We found a protective effect of the CDH1 -160AA and CA + AA polymorphisms for CRC in European and American population (OR = 0.87, 95% CI: 0.76-0.99 and OR = 0.91, 95% CI: 0.85-0.98, respectively). We observed that the CDH1 -347 G/GA + GA/GA carrier had an increased risk of CRC, the summary OR was 1.33 (95% CI: 1.08-1.62). CONCLUSIONS: Data indicated that certain CDH1 gene promoter -160 C > A and -347 G > GA variants might affect the susceptibility of CRC. Recommendations for further studies include pooling of individual data to facilitate evaluation of multigenic effects and detailed analysis of effect modification by environmental and lifestyle factors.

Biomarkers of chromosomal damage in peripheral blood lymphocytes induced by polycyclic aromatic hydrocarbons: a meta-analysis.

BACKGROUND: A crucial early event in polycyclic aromatic hydrocarbons (PAHs) carcinogenesis is the induction of genomic instability phenotype that initiates the progression of a proliferative cell into a cancer cell. However, epidemiological results have been inconsistent. OBJECTIVES: To assess reported studies of associations between the levels of chromosomal damage including sister chromatid exchange (SCE), chromosomal aberrations (CA), and cytokinesis-block micronucleus (CBMN) in peripheral blood lymphocytes and occupational exposure to PAHs. METHODS: Meta-analysis on the association between chromosomal damage and occupational exposure to PAHs was performed with STATA 10.0 software package and Review Manager 4.2.10 in this study. RESULTS: We found statistically significant differences in the frequencies of SCE, CBMN, and CA (aberrations per 100 cells) in peripheral blood lymphocytes between PAHs-exposed group and control group, and the summary estimates of weighted mean difference were 1.42 (95% CI: 0.82-2.02), 1.22 (95% CI: 0.33-2.10), and 0.96 (95% CI: 0.37-1.56), respectively. CONCLUSIONS: Data indicate that the frequencies of SCE, CBMN, and CA (aberrations per 100 cells) in peripheral blood lymphocytes might be indicators of early genetic effects for occupationally PAHs-exposed population.

Association between CYP2E1 genetic polymorphisms and lung cancer risk: a meta-analysis.

Genetic variations in metabolic genes are thought to modify the metabolic process of carcinogens and are suggested to be related to cancer risk. However, epidemiological results are not always consistent. In this meta-analysis, we assessed reported studies of associations between polymorphisms of CYP2E1 RsaI/PstI and DraI, and the risk of lung cancer. We found decreased lung cancer risk among subjects carrying CYP2E1 RsaI/PstI c1/c2 and c1/c2+c2/c2 genotype [odds ratio (OR)=0.80, 95% confidence interval (CI): 0.72-0.89 and OR=0.82, 95% CI: 0.72-0.93, respectively], using 4436 cases and 6385 controls from 26 studies. We also observed a decreased lung cancer risk among subjects carrying c1/c2 and c1/c2+c2/c2 genotypes in the Asian population and on the basis of population control in stratified analysis. We found a protective effect of the CYP2E1 DraI CC and CD+CC polymorphisms for lung cancer (OR=0.58, 95% CI: 0.41-0.81 and OR=0.84, 95% CI: 0.73-0.96, respectively). The meta-analysis suggests that CYP2E1 RsaI/PstI and DraI polymorphisms may affect the susceptibility of lung cancer, and a study with a larger sample size is needed to further evaluate gene-environment interaction on CYP2E1 polymorphisms and lung cancer risk.