长非编码RNA TRALA1调控乳腺癌他莫昔芬耐药的机制研究

Estrogen receptor positive breast cancer constitudes 60%~70% of all breast.cancer. Tamoxifen is the olderst and one of the most frequently used drugs in endocrine treatment. Although most ER positive breast cancer patients respond to tamoxifen, about one third of these patients develop endocrine resistance and eventually relapse. Many studies have demonstrated long non-coding RNAs (lncRNAs) play an important role in the carcinogenesis and development of breast cancer. However, only a few studies investigated the role of lncRNA in endocrine resistance. Our preliminary work identified a lncRNA, TRALA1, played an important role in tamoxifen resistance. In the tamoxifen-resistant breast cell lines, down-regulating the expression of TRALA1 reversed the resistance to tamoxifen. We plan to further explore the function and mechanism of TRALA1 in regulating breast cancer endocrine resistance.

雌激素受体(ER)阳性的乳腺癌占全部乳腺癌的60-70%，虽然ER阳性乳腺癌大多对以他莫西芬为主的内分泌治疗敏感，但仍有三分之一左右的患者会产生耐药并复发，导致疾病进展为不可治愈的转移性乳腺癌。已有较多研究发现，长非编码RNA与乳腺癌的发生发展密切相关，但是长非编码RNA在乳腺癌内分泌耐药中的作用和机制尚不明确。本课题组前期研究发现，一条既往未在乳腺癌中报道过的长非编码RNA TRALA1在乳腺癌他莫昔芬耐药中起着重要作用。在课题组建立的乳腺癌他莫昔芬耐药株中TRALA1表现出明显的上调，敲除TRALA1的表达能够明显逆转乳腺癌的耐药，提示该长非编码RNA能够调控乳腺癌的他莫昔芬耐药。我们拟从TRALA1调控乳腺癌他莫昔芬耐药的生物学现象入手，研究TRALA1在乳腺癌他莫昔芬的具体机制。

雌激素受体(ER)阳性的乳腺癌占全部乳腺癌的60-70%，虽然ER阳性乳腺癌大多对以他莫西芬为主的内分泌治疗敏感，但仍有三分之一左右的患者会产生耐药并复发，导致疾病进展为不可治愈的转移性乳腺癌。该项目自启动以来，围绕激素受体阳性乳腺癌内分泌耐药，cdk4/6抑制剂耐药和激素受体阳性及三阴乳腺癌精准治疗领域展开研究并取得了突破性进展，共发表标注本基金号的SCI论文8篇，单篇最高影响因子17.694。项目负责人已经获得发明授权专利一项，申请专利一项，具有重大转化价值。针对部分研究结果已设计了相应临床试验，目前处于入组中，有望应用于临床，改善乳腺癌患者预后，延长乳腺癌患者生存。