DNA methylation of the RIZ1 tumor suppressor gene plays an important role in the tumorigenesis of cervical cancer

ABTRACT: OBJECTIVE: The retinoblastoma protein-interacting zinc finger gene RIZ1 is a tumor suppressor gene and a member of a nuclear histone/protein methyltransferase superfamily. The purpose of the present study was to examine the expression of RIZ1 and evaluate its carcinogenesis in cervical cancer. The relationship between DNA methylation and transcriptional silencing of RIZ1 was investigated in cervical cancer. METHODS: RIZ1 expression was examined in cervical cancer cell lines and cervical tissues (12 normal and 40 cancerous) by using RT polymerase chain reaction (PCR). Methylation status of the RIZ1 promoter was studied using methylation-specific PCR (MSP). RESULTS: RIZ1 expression is reduced or lost in cervical cancers, compared with normal cervical tissues (P < 0.05). The current study results also showed that loss of RIZ1 is mediated by aberrant cytosine methylation of the RIZ1 promoter. 37.5% of carcinomas were methylated, while none of normal tissues were methylated. RIZ1 mRNA expression was significantly higher (P = 0.000) in unmethylated (0.3494 ± 0.0466, mean ± SD), compared with methylated tissues (0.1422 ± 0.1073, mean ± SD). Treatment with a DNA methyltransferase inhibitor led to reactivation of RIZ1 expression in cell lines that had negligible RIZ1 expression at baseline. CONCLUSIONS: Reduced expression of RIZ1 may play an important role in the pathogenesis and/or development of cervical cancer, and is considered to be caused in part by aberrant DNA methylation.