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.