Department of Gynecologic Oncology, The Tumor Hospital of Harbin Medical University, Heilongjiang, 150081, China.
Eur J Med Res. 2010 Jan 29;15(1):20-4. doi: 10.1186/2047-783x-15-1-20.
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.
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).
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.
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.
视网膜母细胞瘤蛋白相互作用锌指基因 RIZ1 是一种肿瘤抑制基因，也是核组蛋白/蛋白质甲基转移酶超家族的成员。本研究旨在研究 RIZ1 的表达，并评估其在宫颈癌中的致癌作用。研究了宫颈癌中 RIZ1 的 DNA 甲基化与转录沉默的关系。
采用 RT-PCR 检测宫颈癌细胞系和宫颈组织（正常 12 例，癌 40 例）中 RIZ1 的表达。采用甲基化特异性 PCR（MSP）研究 RIZ1 启动子的甲基化状态。
与正常宫颈组织相比，宫颈癌中 RIZ1 的表达降低或缺失（P<0.05）。本研究结果还表明，RIZ1 的缺失是由 RIZ1 启动子的异常胞嘧啶甲基化介导的。37.5%的癌组织发生甲基化，而正常组织均未发生甲基化。未甲基化组织（0.3494 +/- 0.0466，均值 +/-SD）的 RIZ1 mRNA 表达明显高于甲基化组织（0.1422 +/- 0.1073，均值 +/-SD）（P = 0.000）。用 DNA 甲基转移酶抑制剂处理后，基线时 RIZ1 表达极低的细胞系中 RIZ1 表达得到了重新激活。
RIZ1 表达降低可能在宫颈癌的发病机制和/或发展中发挥重要作用，部分原因被认为是异常的 DNA 甲基化所致。
