Frequent Increased Gene Copy Number and High Protein Expression of tRNA (Cytosine-5-)-Methyltransferase (NSUN2) in Human Cancers
Frequent Increased Gene Copy Number and High Protein Expression of tRNA (Cytosine-5-)-Methyltransferase (NSUN2) in Human Cancers
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DOI：
10.1089/dna.2011.1446
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发表时间：
2012-05-01
影响因子：
3.1
通讯作者：
Tatsuka, Masaaki
中科院分区：
文献类型：
--
作者：
Okamoto, Mayumi;Hirata, Sumi;Tatsuka, Masaaki
NSUN 2，也称为萨基或MISU，是一种甲基转移酶，催化tRNA的（胞嘧啶-5-）-甲基化。人类NSUN 2基因位于染色体5p15.31-33。我们发现，在口腔癌和结直肠癌中，NSUN 2基因拷贝数增加。使用针对对应于蛋白质C-末端区域的合成肽产生的新型多克隆抗体，通过免疫印迹测定NSUN 2的蛋白质表达水平。在大多数正常组织中，NSUN 2表达水平极低。另一方面，口腔癌和结直肠癌通常表达高水平的NSUN 2。NSUN 2的水平在间期细胞和有丝分裂细胞中相似，免疫组化分析表明，与正常组织相比，口腔癌和结肠癌组织中的NSUN 2染色较强，与Ki-67相比，NSUN 2具有明显的诊断意义，Ki-67是一种广泛使用的活跃增殖细胞的标志物。此外，通过对各种癌症包括食管癌、胃癌、肝癌、胰腺癌、宫颈癌、前列腺癌、肾癌、膀胱癌、甲状腺癌和乳腺癌的免疫组织化学分析证实了NSUN 2蛋白表达的升高。NSUN 2受Aurora-B调控，Aurora-B是一种新开发的肿瘤治疗分子靶点，这使我们提出NSUN 2可能成为一种有价值的肿瘤治疗靶点和肿瘤诊断标志物。
NSUN2, also known as SAKI or MISU, is a methyltransferase which catalyses (cytosine-5-)-methylation of tRNA. The human NSUN2 gene is located on chromosome 5p15.31-33. We show that NSUN2 gene copy number is increased in oral and colorectal cancers. Protein expression levels of NSUN2 were determined by immunoblot using novel polyclonal antibodies raised against a synthetic peptide corresponding to the C-terminal region of the protein. In most normal tissues, NSUN2 expression levels were extremely low. On the other hand, oral and colorectal cancers typically expressed high levels of NSUN2. The level of NSUN2 was similar in interphase and mitotic cells, and immunohistochemical analysis demonstrated strong staining for NSUN2 in oral and colon cancer tissues when compared with normal tissues, providing a distinct diagnostic significance for NSUN2 in comparison with Ki-67, a widely used marker of actively proliferating cells. In addition, elevated protein expression of NSUN2 was confirmed by immunohistochemical analysis of various cancers including esophageal, stomach, liver, pancreas, uterine cervix, prostate, kidney, bladder, thyroid, and breast cancers. NSUN2 is regulated by Aurora-B, a newly developed molecular target for cancer therapy, leading us to propose that NSUN2 might become a valuable target for cancer therapy and a cancer diagnostic marker.