miR-423在乳腺癌恶性转移过程中的作用和调控机制研究

肿瘤是否转移是由肿瘤细胞本身遗传特征以及其肿瘤微环境的特点来共同决定的。近年来研究发现一些miRNAs既有调控肿瘤细胞生物学行为的功能又能通过调节肿瘤微环境的特点来促进肿瘤的恶性转移。我们最近发现在发生转移的乳腺癌病人的肿瘤组织中miR-423高表达，在体外细胞实验中该miR不仅能促进肿瘤细胞的增殖和迁移，而且能分泌到细胞培养液中，并且在体外细胞实验中该miR能显著促进血管内皮细胞的迁移和成管。在本项申请中，申请者将确定miR-423促进肿瘤细胞增殖和迁移的分子机制；利用SCID小鼠来研究miR-423在肿瘤转移中的作用；在临床样本中探究miR-423及其靶基因的表达情况。上述实验，将为miR-423在人类乳腺癌模型中作为治疗靶点，早期诊断的标志物及预后判断的可能性提供实验依据。

Metastasis is a complex process that requires cancer cells to escape from the primary tumor, survive in the circulation, and adapt to a new environment at the distant sites for survival and proliferation. Each of these processes, cancer cells closely interact with their surrounding microenvironment. Indeed, it is widely accepted that the metastasis potential of cancer cells is determined by their intrinsic and extrinsic properties and the role of miRs has been implicated in regulating both to promote metastasis. Our preliminary study showed that miR-423 is highly expressed in the metastatic breast tissues. Further analysis showed that miR-423 altered the intrinsic properties of cancer cells such as cell proliferation and migration. And furthermore, our preliminary data suggested that it actively involved in the formation of tumor associated angiogenesis. In this application we aim to: 1)determine the molecular mechanism of miR-423 in the regulation of cancer cell proliferation and migration; 2)study the function of miR-423 in xenograted SCID mice; 3)determined the molecular mechanism of miR-423 in the regulation of tumor asscociated angiogenesis; 4)evaluate its potential as a diagnostic biomaker for breast cancer metastasis.