子宫内膜癌是常见的妇科恶性肿瘤, 严重威胁妇女身心健康。近年来，研究发现中电导钙激活钾离子通道（KCa3.1）参与多种肿瘤的转移，其作用机制尚不清楚。申请者根据前期在子宫内膜癌中对KCa3.1功能和启动子胞嘧啶甲基化和羟甲基化修饰的研究结果，提出以下猜想：在子宫内膜癌转移过程中，长链非编码RNA（LncRNA） TANCT1通过序列互补原理特异性地招募DNA羟甲基化酶Tet1到KCa3.1的启动子区域，将胞嘧啶甲基化位点修饰为羟甲基化，从而调控KCa3.1的甲基化修饰过程和上调KCa3.1的表达，促使钙离子内流并影响膜电位，促进细胞的增殖、侵袭和转移。课题拟从细胞、动物和临床三个层面探索TANCT1与Tet1酶的结合方式、对KCa3.1转录表达的影响及在子宫内膜癌转移中的作用，评价TANCT1作为子宫内膜癌转移和预后分子标志物的可能性。

Endometrial carcinoma is one of the most common gynecological cancers. KCa3.1 plays an important role in the metastasis of cancers with unclear mechanism. Based on the results of our previous research of KCa3.1, methylation and hydroxymethylation modification in its promoter cytosine modification mediated by Tet1 binding LncRNA TANCT1, we propose the hypothesis that LncRNA TANCT1 exert its function of regulating methylation-hydroxymethylation transformation via direct recruiting Tet1, which results in the hydroxymethylation of methylated cytosine in KCa3.1 gene promoter CpG island and its high expression. The augmented expression of KCa3.1 triggers Ca2+ influx and promotes cells proliferation and migration and induces endometrial carcinoma metastasis. In the following study, we intend to explore the function of TANCT1 in the process of KCa3.1 gene promoter CpG island hydroxymethylation, study the mechanism how TANCT1 recruits Tet1 and evaluate the role of TANCT1 as biomarker for the prognosis of endometrial carcinoma. The research would provide basis and potential target for therapy of endometrial carcinoma.