Huang Yuji, Wang Guanghui, Liang Zhonglin, Yang Yili, Cui Long, Liu Chen-Ying
Department of colorectal and anal surgery, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
Shanghai Colorectal Cancer Research Centre, Shanghai, China.
Clin Epigenetics. 2016 Jan 26;8:9. doi: 10.1186/s13148-016-0176-7. eCollection 2016.
5-Hydroxymethylcytosine (5hmC) is lost in multiple human cancers, including colorectal cancer (CRC). Decreased ten-eleven translocation 1 (TET1) messenger RNA (mRNA), but not other two TET family members, has been observed in the colorectal cancer and is crucial for colorectal cancer initiation. Here, we show that nuclear localization of TET2 was lost in a significant portion of CRC tissues, in association with metastasis. In CRC cells, nuclear expression of TET2 were absent but not TET3. Nuclear export inhibitor can increase the 5hmC level in CRC cells, probably through regulating TET2. Our results indicate a new mechanism of TET2 dysregulation in colorectal cancer.
5-羟甲基胞嘧啶（5hmC）在包括结直肠癌（CRC）在内的多种人类癌症中缺失。在结直肠癌中已观察到十一-易位酶1（TET1）信使核糖核酸（mRNA）水平降低，而其他两个TET家族成员则未出现这种情况，且TET1对结直肠癌的发生至关重要。在此，我们发现TET2的核定位在相当一部分CRC组织中缺失，且与转移相关。在CRC细胞中，TET2无核表达，但TET3有核表达。核输出抑制剂可能通过调节TET2来提高CRC细胞中的5hmC水平。我们的结果表明了结直肠癌中TET2失调的一种新机制。
