Wang Kuo-Chiang, Kang Chi-Hsiang, Tsai Chung-Yu, Chou Nan-Hua, Tu Ya-Ting, Li Guan-Cheng, Lam Hing-Chung, Liu Shiuh-Inn, Chang Po-Min, Lin Yan-Hwai, Tsai Kuo-Wang
Division of General Surgery, Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan, R.O.C.
Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan, R.O.C.
Oncol Lett. 2018 Jan;15(1):278-284. doi: 10.3892/ol.2017.7264. Epub 2017 Oct 25.
A sixth base, 5-hydroxymethylcytosine (5hmC), is formed by the oxidation of 5-methylcytosine (5mC) via the catalysis of the ten-eleven translocation (TET) protein family in cells. Expression levels of 5hmC are frequently depleted during carcinogenesis. However, the detailed mechanisms underlying the depletion of 5hmC expression in gastric cancer cells remains unclear, and further research is required. The present study examined the expression levels of 5mC and 5hmC and the expression levels of TET1 and TET2 in gastric cancer tissues using immunohistochemistry. The results revealed that 5hmC expression levels were markedly lower in gastric cancer tissues compared with corresponding adjacent normal tissues. Furthermore, a decrease in 5hmC expression levels was associated with a decrease in TET1 protein expression levels in gastric cancer tissues. The ectopic expression level of TET1 may increase the 5hmC expression level in gastric cancer cells. In addition, the results revealed that TET1 protein expression was markedly different in regards to subcellular localization, and mislocalization was significantly associated with the depletion of 5hmC expression levels in gastric cancer. Together, the results of the present study indicated that TET1 dysfunction reduces 5hmC expression levels, and this phenomenon may serve a crucial role in gastric cancer progression.
第六种碱基，5-羟甲基胞嘧啶（5hmC），是由细胞中的十一易位（TET）蛋白家族催化5-甲基胞嘧啶（5mC）氧化形成的。在致癌过程中，5hmC的表达水平经常降低。然而，胃癌细胞中5hmC表达降低的详细机制仍不清楚，需要进一步研究。本研究采用免疫组织化学方法检测了胃癌组织中5mC和5hmC的表达水平以及TET1和TET2的表达水平。结果显示，与相应的癌旁正常组织相比，胃癌组织中5hmC的表达水平明显较低。此外，胃癌组织中5hmC表达水平的降低与TET1蛋白表达水平的降低有关。TET1的异位表达水平可能会增加胃癌细胞中5hmC的表达水平。此外，结果显示TET1蛋白表达在亚细胞定位方面存在明显差异，并且定位错误与胃癌中5hmC表达水平的降低显著相关。本研究结果共同表明，TET1功能障碍会降低5hmC表达水平，这种现象可能在胃癌进展中起关键作用。
