Abstract. Promoter methylation of the RASSF1A and RARβ genes has been associated with susceptibility to different types of cancer. In addition, RASSF1A and RARβ methylation plays an important role in the pathogenesis of lung cancer. We investigated the aberrant promoter methylation of RASSF1A and RARβ in lung cancer patients using methylation-specific polymerase chain reaction (MSP). Aberrant promoter methylation of the RASSF1A gene was detected in 45 of 56 (80.36%) cancer patients and aberrant promoter methylation of the RARβ gene was found in 48 of 56 (85.71%) cases; promoter methylation of both genes was found in 42 of 56 (75%) lung cancer cases. None of the 52 samples from controls exhibited DNA methylation in these two target genes. Methylation was significantly associated with the lung cancer cases compared to controls for the RASSF1A gene (adjusted OR=7.50; 95% CI, 3.935-14.296; p<0.001); similar results were obtained for methylation of the RARβ gene (adjusted OR=5.727; 95% CI, 3.348-9.797; p<0.001). In addition, the association remained significant in these two target genes (adjusted OR=8.429; 95% CI, 4.205-16.896; p<0.001). Our results indicated that the high percentage of promoter methylation in the RARβ and RASSF1A genes indicate their important role in the development of lung cancer in the population studied, and that risk of lung cancer for carriers positive for both genes is higher than in single-gene positive carriers, which may serve as a useful marker for prognosis and a target for the treatment of lung cancer.

Epigenetic modifications of tumour suppressor genes are involved in all kinds of human cancer. Aberrant promoter methylation is also considered to play an essential role in development of lung cancer, but the pathogenesis remains unclear.We collected the data of 112 subjects, including 56 diagnosed patients with lung cancer and 56 controls without cancer. Methylation of the FHIT, RASSF1A and RAR-β genes in DNA from all samples and the corresponding gene methylation status were assessed using the methylation-specific polymerase chain reaction (PCR, MSP). The results showed that the total frequency of separate gene methylation was significantly higher in lung cancer compared with controls (33.9-85.7 vs 0 %) (p<0.01).Similar outcomes were obtained from the aberrant methylation of combinations of any two or three genes (p<0.01). There was a tendency that the frequency of combinations of any two or three genes was higher in stageⅠ+Ⅱ than that in stage Ⅲ+Ⅳ with lung cancer. However, no significant difference was found across various clinical stages and clinic pathological gradings of lung cancer (p>0.05).These observations suggest that there is a significant association of promoter methylation of individual genes with lung cancer risk, and that aberrant methylation of combination of any two or three genes may be associated with clinical stage in lung cancer patients and involved in the initiation of lung cancer tumorigenesis. Methylation of FHIT, RASSF1A and RARβ genes may be related to progression of lung oncogenesis.

Abstract. The present study aimed to investigate the association of p73 G4C14-A4T14 polymorphism and murine double minute 2 (MDM2) 309 T/G single nucleotide polymorphisms (SNPs) with the risk of developing non-small cell lung cancer (NSCLC) in Sothern China. The p73 and MDM2 genotypes of peripheral blood DNA from 186 patients with NSCLC and 196 normal controls were detected by polymerase chain reaction (PCR) with confronting two-pair primers (CTPP) and high resolution melting (HRM), respectively. The results of genotyping were consistent with those of direct sequencing. The p73 AT/AT [odds ratio (OR)=0.46; 95% confidence interval (CI)=0.22-0.97] and MDM2 TT (OR=0.48; 95% CI=0.26-0.86) genotypes were associated with a decreased risk of developing NSCLC compared with that of the p73 GC/GC and MDM2 GG genotypes, respectively. In addition, the interaction between the p73 and MDM2 polymorphisms reduced the risk of developing NSCLC in multiple ways (OR=0.13; 95% CI=0.03-0.59) for subjects carrying both the p73 AT/AT and MDM2 TT genotypes. Therefore, the SNP in p73 G4C14-A4T14 and the MDM2 309 polymorphism may be markers of genetic susceptibility to NSCLC in a Chinese population, and there is a possible gene-gene interaction involved in the incidence of NSCLC. IntroductionNon-small cell lung cancer (NSCLC), the main type of lung cancer, is one of the most common malignant tumors in males worldwide (1). The incidence and mortality of lung cancer is currently increasing in China, and the most common risk factors are involved environmental, occupational and genetic (2-4). Environmental factors, including tobacco smoking, air pollution, contamination in drinking water and food, are passing through the natural barriers such as shin and metabolic elimination; the environmental carcinogens enter cells, damage DNA and destroy the balance among growth, differentiation and apoptosis of the cells, which cause carcinogenesis (3,4).It has been well established that lung cancer is a complex disease that is highly correlated with environmental pollutants in the general population; in addition, genetic factors are known to plays an important role in this disease (2-4). Studies on the association between gene variants and lung cancer will contribute to clarify the underlying mechanisms of lung cancer, including its development, and will potentially provide therapeutic targets that are important in the diagnosis and prognosis of lung cancer.p73, one of the p53 family members, is located at the human chromosome 1p36.33, and shares relatively high structural and functional homology with p53 (5,6). As a candidate tumor-suppressor gene, it encodes two different proteins, namely the transcriptionally active full-length TAp73 and the NH 2 terminally truncated dominant-negative ΔNp73 (6), which have remarkable similarity with p53 in their DNA-binding, transactivation and oligomerization domains (5). G4C14 and A4T14, the two single nucleotide polymorphisms (SNPs) of p73 at positions 4 (G>A) and 14 (C>T) (rs2273953 and rs1801173, respectively), ...

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Titanium dioxide nanoparticles (TiO2-NPs) are widely used for biomedical and food applications, the toxicity of TiO2-NPs in vivo and in vitro has been elucidated, but the underlying cytotoxicity of TiO2-NPs against microRNA remains largely unknown. The purpose of this study was to analyze microRNA profiling induced by TiO2-NPs against NCM460 and HCT116 cell lines. Comparative analysis identified 34 and 24 microRNAs were significantly altered in the TiO2-NPs treated cells at concentrations of 3 μg/mL and 30 μg/mL, respectively. Functional classification demonstrated that a large proportion of genes involved in metabolism, human disease, and environmental information process were significantly upregulated by TiO2-NPs. Bioinformatics analysis suggested that microRNA 378 might be an early indicator of cellular response to exogenous stimuli with apoptotic signals. Furthermore, TiO2-NPs significantly altered the expression of microRNA 378b and 378g in HCT116 and NCM460 cell lines at different concentrations from 3 to 6 μg/mL. These concentrations elicit high-sensitivity of stimuli response in colon cancer cells when exposed to the slight doses of TiO2-NPs. Our study indicated that microRNAs 378b and 378g may play an important role in TiO2-NPs-mediated colonic cytotoxicity, which may provide a valuable insight into the molecular mechanisms of potential risks in colitis and colon cancer.

Monascus pigments (MPs), as secondary metabolites of Monascus, are microbial pigments which have been used for thousands of years. MPs are widely used in food industry as food pigments and preservatives, which have the stability of light resistance, high temperature resistance and acid-base change resistance. In addition, the antioxidant, antibacterial, antiviral and anti-tumor biological activities of MPs have also attracted people’s attention. Moreover, Due to the presence of citrinin, the safety of MPs still needs to be discussed and explored. In this paper, the production, biological activity, application in various fields and methods of detection and reduction of citrinin of MPs were reviewed, which provide new insights into the study and safe application related to human different diseases, medicines or health care products with MPs as active substances.

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