甲硫氨酸腺苷转移酶 2A 在肾细胞癌中的表达及其在肾癌发生中的潜在机制。
Expression of methionine adenosyltransferase 2A in renal cell carcinomas and potential mechanism for kidney carcinogenesis.
机构信息
Shenzhen Key Laboratory of Genitourinary Tumor, Shenzhen Second People's Hospital, First Affiliated Hospital of Shenzhen University, Shenzhen 518035, Guangdong, China.
出版信息
BMC Cancer. 2014 Mar 17;14:196. doi: 10.1186/1471-2407-14-196.
BACKGROUND
Methionine adenosyltransferase 2A (MAT2A) is an enzyme that catalyzes the formation of S-adenosylmethionine (SAMe) by joining methionine and ATP. SAMe is a methyl donor for transmethylation and has an important role for DNA and/or protein methylation. MAT2A is expressed widely in many tissues especially in kidney. Several studies have demonstrated that there are abnormal expressions of MAT2A in several kinds of cancers such as liver and colon cancers. But the relationship of MAT2A between renal cell carcinomas (RCC) is less understood.
METHODS
The mRNA expression level of the MAT2A gene was determined in 24 RCC patients and 4 RCC cell lines, using real-time quantitative-polymerase chain reaction (RT-PCR). The MAT2A protein content was measured by western blotting and immunohistochemical analysis in 55 RCC patients. The mRNA levels of heme oxygenase-1 (HO-1) and cyclooxygenase-2 (COX-2) were also analysized in patients using RT-PCR. The correlations between the MAT2A and HO-1 as well as COX-2 were analyzed with nonparametric Spearman method.
RESULTS
MAT2A transcript was significantly downregulated in cancer tissues compared to normal tissues (P < 0.05). Immunohistochemical analysis and western blotting indicated that level of MAT2A protein was decreased in cancer tissues. The statistical analysis reveals a negative correlation between MAT2A and HO-1 expression in RCC patients and cell lines (P < 0.01).
CONCLUSIONS
This study demonstrated that MAT2A was lower expression in cancer tissues, suggesting that it may be involved in the development of RCC. MAT2A is a transcriptional corepressor for HO-1 expression by supplying SAM for methyltransferases, which may be one of potential mechanism of MAT2A as tumor suppressor in kidney carcinogenesis.
背景
甲硫氨酸腺苷转移酶 2A（MAT2A）是一种酶，通过将蛋氨酸和 ATP 结合起来催化 S-腺苷甲硫氨酸（SAMe）的形成。SAMe 是转甲基作用的甲基供体，对 DNA 和/或蛋白质甲基化有重要作用。MAT2A 在许多组织中广泛表达，尤其是在肾脏中。几项研究表明，MAT2A 在几种癌症（如肝癌和结肠癌）中存在异常表达。但是，MAT2A 与肾细胞癌（RCC）之间的关系了解较少。
方法
使用实时定量聚合酶链反应（RT-PCR）测定 24 例 RCC 患者和 4 个 RCC 细胞系中 MAT2A 基因的 mRNA 表达水平。通过 Western blot 和免疫组织化学分析测定 55 例 RCC 患者中 MAT2A 蛋白含量。使用 RT-PCR 分析患者中血红素加氧酶-1（HO-1）和环氧化酶-2（COX-2）的 mRNA 水平。使用非参数 Spearman 方法分析 MAT2A 与 HO-1 和 COX-2 之间的相关性。
结果
与正常组织相比，癌症组织中 MAT2A 转录本明显下调（P <0.05）。免疫组织化学分析和 Western blot 表明，MAT2A 蛋白水平在癌症组织中降低。统计分析表明，在 RCC 患者和细胞系中，MAT2A 与 HO-1 表达之间呈负相关（P <0.01）。
结论
本研究表明，MAT2A 在癌症组织中表达较低，提示其可能参与 RCC 的发生。MAT2A 通过为甲基转移酶提供 SAM 作为 HO-1 表达的转录核心抑制剂，这可能是 MAT2A 作为肾脏癌发生中肿瘤抑制因子的潜在机制之一。
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