MiR-449介导KDM4C-Notch通路在三阴性乳腺癌增殖转移中的调控研究

项目名称： MiR-449介导KDM4C-Notch通路在三阴性乳腺癌增殖转移中的调控研究

项目编号： No.U1204821

项目类型： 联合基金项目

立项/批准年度： 2013

项目学科： 肿瘤学2

项目作者： 刘刚

作者单位： 河南科技大学

项目金额： 30万元

中文摘要： 三阴性乳腺癌（ER、PR和HER-2均阴性，TNBC）侵袭性强、预后差。与ER阳性或HER-2阳性乳腺癌相比，缺乏较有效的治疗选择与靶向药物。我们发现：TNBC中多有KDM4C的扩增与高表达，"DM4C-Notch"通路的异常激活与其恶性生物学行为有关。TargetScan软件预测可能调控KDM4C的miRNA,仅发现miR-449是特异性候选miRNA。预实验miR-449在临床TNBC样本中的表达明显低于癌旁正常乳腺组织。因此推测miR-449可能通过调控其靶基因KDM4C从而影响TNBC增殖与转移。本研究拟检测TNBC组织与乳癌细胞系miR-449、KDM4C的表达及相关性；并分别对miR-449高表达和低表达乳腺癌细胞系抑制和转染miR-449，观察增殖、侵袭和迁移、SCID小鼠检测成瘤和转移变化。阐明miR-449调控KDM4C在TNBC增殖转移中的机制提供实验基础和理论依据。

中文关键词： 三阴性乳腺癌；miR-449；KDM4C；增殖；转移

英文摘要： Triple-negative breast cancer (TNBC), defined by a lack of expression of both estrogen and progesterone receptor (ER,PR) as well as human epidermal growth factor receptor 29(HER-2). TNBC represents an important clinical challenge characterized by high invasiveness and poor clinical prognosis, because these cancers do not respond to endocrine therapy or other available targeted agents. In our previous studies, KDM4C gene is amplified and overexpressed in TNBC, which is positively correlated with the clinical stage and distant metastasis status. Activation of “KDM4C-Notch” pathway may related to the malignant behavior of TNBC. To investigate the microRNAs which may regulate KDM4C, TargetScan software was used and predicted that miR-449 may be the one and specific miRNA that regulate KDM4C. Our preliminary experiment also showed that the expression of miR-449 in clinical TNBC specimen is significantly lower than normal breast tissue. Therefore, we speculate that miR-449 may directly regulate its target gene-KDM4C,by doing so, influence the proliferation and metastasis of TNBC. In this study, the expression and correlation of miR-449 and KDM4C will be validated in TNBC samples and breast cancer cell lines by real-time quantitative PCR and Western blot. Further, to clarify the regulatory mechanism of miR-449 for KDM4

英文关键词： Triple-negative breast cancer (TNBC)；miR-449；KDM4C；proliferation；metastasis