lncRNA DATOC1影响microRNA成熟促进卵巢癌转移的分子机制研究

项目名称： lncRNA DATOC1影响microRNA成熟促进卵巢癌转移的分子机制研究

项目编号： No.81502260

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 秦文星

作者单位： 中国人民解放军第二军医大学

项目金额： 16万元

中文摘要： 转移是卵巢癌诊治中的棘手问题，研究lncRNA在转移中的作用对转移性卵巢癌的诊治具有重要意义。. 我们发现：卵巢癌转移样本中高表达的lncRNA DATOC-1能与DICER酶结合从而调控一类具有抑癌表型的microRNA成熟体表达显著下调，这些抑癌microRNA多数靶向MMP家族蛋白。于是，申请者提出DATOC-1通过与DICER酶特异性的结合、抑制DICER酶功能，从而下调mDDSM系列microRNA成熟，提高MMP家族蛋白表达，进而促进卵巢癌转移的假说。项目后续将通过动物模型观察DATOC-1对卵巢癌转移的影响,通过RIP-seq、蛋白截断等手段研究DATOC-1与DICER酶的结合以及对mDDSM系列microRNA及MMP家族的调控。. 该项目创新性地提出lncRNA分子调控DICER酶功能的理论假说，所得研究结果有望为转移性卵巢癌的诊治提供新的方向。

中文关键词： 卵巢肿瘤；转移；长链非编码RNA

英文摘要： Metastasis is one of the most intractable problems for the treatment of ovarian cancer. The research of molecular mechanism on ovarian cancer metastasis will provide theoretical basis for developing pharmaceuticals used for the novel diagnostic biomarkers and intervention of ovarian cancer. Based on previous work, lncRNA DATOC-1 was screened by lncRNA microarray and DICER RIP-seq. In vitro ovarian cancer cell line knockdown of DATOC-1 demonstrated declined proliferation and migration capability. Subsequent small RNA sequencing of microRNAs illustrate that a small cohort of microRNAs with tumor-suppressive characteristics named as mDDSM expression was significantly high in the mature form and premature counterpart. Based on previous results, novel theory of up-regulated lncRNA DATOC-1 interacting with DICER to participate in the process of microRNAs maturation was put forward. The project will explore the in vivo and in vitro function of DATOC-1 during ovarian cancer metastasis and downward molecular mechanism underlying the oncogenic function and evaluate the biomarker performance of DATOC-1 on the early diagnosis of ovarian cancer metastasis and prognosis of patients’ survival. The project will provide a new way of ovarian cancer diagnosis and intervention.

英文关键词： ovarian cancer;metastasis;lncRNA