miR-130b可能通过抑制全基因组miRNA合成关键酶促进子宫内膜癌的增殖与转移

与雌激素拮抗的孕激素治疗子宫内膜癌（内膜癌）的客观反应率低，以及PTEN基因下游mTOR抑制剂雷帕霉素不能有效阻断内膜癌细胞增殖，提示内膜癌的发生存在除雌激素刺激和PTEN失活之外的转录后调控重要机制。课题组预实验初步结果表明，具有核糖核酸内切酶功能的DICER1通过控制内膜癌细胞下游全基因组微小RNA成熟过程，显著抑制肿瘤细胞的增殖和侵袭能力；软件预测DICER1可能是miR-130b的靶基因。课题在预实验基础上检测内膜癌中DICER1失活对内膜癌细胞播散及转移的影响；验证miR-130b对理论靶基因DICER1的调控作用；探讨miR-130b调控DICER1对内膜癌生物学行为影响的机制，旨在证实miR-130b通过抑制DICER1表达，从而促进内膜癌复发及转移的机制。研究将在理论上加深对内膜癌复发及转移机制的理解，为个体化分子靶向治疗提供坚实的实验依据。

The response rate of opposed-estrogen (mainly progestins) therapy is low in patients with endometrial cancer.And rapamycin, which is a kind of mTOR inhibitor located downstream of PTEN gene, can not effectively block the proliferation of endometrial cancer cells. All these indicate the posttranscription regulation play an important role in the initiation of endometrial cancer besides unopposed estrogen stimulation and inactivation of PTEN gene. We found the expression of DICER1, a key component of the micro-RNA(miRNA) processing machinery,can significantly inhibit the proliferation and invasion ability of tumor cells through controlling its downstream miRNAs mature in endometrial cancer.The softwares forecast DICER1 may be one of the target genes of miR-130b. Subject on the basis of preliminary results, we further investigate the role of DICER1 inactivation in endometrial cancer spread and metastasis. We also try to illucidate that miR-130b target DICER1 and the role of miR-130b-DICER1 axis in the biological behavior of endometrial cancer. We are aiming to prove that miR-130b promotes endometrial cancer relapse and metastasis by targeting DICER1.Our research tries to deepen the understanding of the mechanism of endometrial cancer recurrence and metastasis in theory, and provides solid experimental basis for individualized molecular targeted therapy.