乳腺癌肺转移相关microRNA的筛选及功能分析

乳腺癌是全球女性最常见的恶性肿瘤之一，复发转移是导致乳腺癌患者死亡的主要原因，尤以肺转移发生率最高。近年来，microRNA的出现为肿瘤的研究提供了崭新的思路，但是目前对于调控乳腺癌发生肺转移的microRNA却知之甚少。为找到调控乳腺癌肺转移的microRNA，我们构建了乳腺癌肺高转移能细胞系，运用microRNA芯片筛选出与肺转移密切相关的microRNAs并进行验证，最终确立了5个候选microRNAs作为我们深入研究的目标。本项目拟通过过表达和干扰microRNA进行体内外实验，分析其对乳腺癌细胞增殖、浸润转移及血管新生的影响，明确其靶基因并探讨其分子通路。然后通过检测相关microRNA在良恶性乳腺组织中的表达情况以明确其临床应用价值。本课题的完成将有助于阐明乳腺癌进展转移过程中候选microRNAs所起的作用，也将为乳腺癌肺转移的防治提供新的靶标。

Breast cancer is one of the most common malignant diseases among women in the world. Relapse and metastasis was the leading cause for the death of patients with breast cancer, especially the lung metastasis. Recently, the emergence of microRNA opens a new avenue for cancer research; however, little is known about the regulatory microRNA for breast cancer lung metastasis. To identify regulatory microRNA for breast cancer lung metastasis, we established two breast cancer cell lines with highly lung metastatic potential and adopted microarray to screen the lung metastasis relevant microRNAs. After validation, we ultimately chose five candidate microRNAs for further investigation. The project intends to clarify the effect of these candidate microRNAs on breast cancer proliferation, invasion, metastasis and angiogenesis in vitro and in vivo. We further identify the target genes of candidate microRNAs and unravel the underlying detailed molecular mechanism in the process of breast cancer metastasis. In order to explore the clinical value of these microRNAs, microRNA expression in the benign and malignant breast cancer tissues will also be analyzed. The results from our project will contribute to elucidate the role of these candidate microRNAs in the process of breast cancer progression and metastasis, and also provide new targets in the prevention and treatment for breast cancer lung metastasis.