[Interaction between abnormal expression of fragile histidine triad and methyl-CpG-binding protein 2 on cervical cancerization].

Objective: To explore the relationship between abnormal expression of fragile histidine triad (FHIT) gene and methyl-CpG-binding protein 2 (MeCP2) as well as their interaction on cervical cancerization. Methods: A total of 73 patients with cervical squamous cell carcinoma (SCC), 113 patients with cervical intraepithelial neoplasia (CIN Ⅰ, n =45; CINⅡ/Ⅲ, n =68) and 60 women with normal cervix (NC) were included in the study. Real time PCR and Western blot were performed to detect the expression levels of mRNA and protein about FHIT and MeCP2, respectively. The methylation status of FHIT gene CpG island was tested by methylation-specifc PCR (MSP). Kruskal-Wallis H test, χ (2) test, trend χ (2) test and Spearman correlation analysis were conducted with software SPSS 20.0. The interaction was evaluated by generalized multifactor dimensionality reduction (GMDR) model. Results: With the deterioration of cervical lesion, the methylation rates of FHIT gene CpG island ( χ (2)=18.64, P <0.001; trend χ (2)=18.08, P <0.001) increased gradually, while the expression levels of FHIT mRNA ( H =27.32, P <0.001; trend χ (2)=12.65, P <0.001) and protein ( H =47.10, P <0.001; trend χ (2)=29.79, P <0.001) decreased gradually. There was a negative correlation between the methylation rates of FHIT gene CpG island and the expression level of FHIT protein ( r =-0.226, P <0.001). The levels of MeCP2 mRNA ( H =26.19, P <0.001; trend χ (2)=11.81, P =0.001) and protein ( H =69.02, P <0.001; trend χ (2)=47.44, P <0.001) increased gradually with the aggravation of cervical lesions. There was a positive correlation between the expression level of MeCP2 protein and the FHIT mRNA Ct ratio ( r =0.254, P <0.001). Expression of proteins were negatively correlated between MeCP2 and FHIT ( r =-0.213, P =0.001). The results analyzed by GMDR model showed that there were interactions among high MeCP2 protein expression, the CpG island methylation of FHIT and mRNA and protein expression in CINⅡ/Ⅲ group, and among high MeCP2 mRNA and protein expression, the CpG island methylation of FHIT and low mRNA and protein expression in SCC group. Conclusion: High expression of MeCP2 mRNA and protein, the CpG island methylation and low mRNA and protein expression of FHIT could increase the risk of cervical carcinogenesis, and there might be a synergistic effect on cervical carcinogenesis.