miR-758在高剂量复合维生素片增加乳腺癌风险中的作用与机制研究

过量摄入多元维生素增加乳腺癌风险已有较多报道，而血管生成是乳腺癌生长、浸润和转移的重要条件。miR-758是我们应用芯片发现的、在长期服用复合维生素片乳腺癌患者内皮细胞中差异表达的miRNA，而miR-758与乳腺癌关系未见报道。实验发现，miR-758沉默可致内皮细胞增殖、转移、形成新管腔，软件预测Ang-2为其靶基因，而高剂量多元维生素能下调内皮细胞中miR-758表达、上调Ang-2表达，提示高剂量多元维生素可能通过miR-758/Ang-2机制促进血管生成而诱发乳腺癌。研究拟从正反两方面论证miR-758在促乳腺癌血管生成中的作用；以Ang-2为切入点，揭示miR-758的分子机制；系统评估高剂量多元维生素通过miR-758/Ang-2机制增加乳腺癌风险的作用。课题从营养与肿瘤关系视角，揭示miR-758在乳腺癌发生中的未知功能与机制，可为乳腺癌的营养学研究提供新线索。

The increasing incidence of breast cancer has been confirmed with excessive consumption of multivitamin, however, angiogenesis plays an important role in its development, invasion and metastasis. miR-758 is screened from miRNA array and expressed differently in the endothelial cells of breast cancer patients with long-term supplement of multivitamin, with rare study between them. The knockdown of miR-758 could accelerate proliferation, migration and tube formation of endothelial cell, and Ang-2 is predicted a target. Our previous study showed that high-dose multivitamin could decrease the expression of miR-758 and increase Ang-2 level; the knockdown of miR-758 could accelerate proliferation, migration and tube formation of endothelial cell, and Ang-2 is targeted by miR-758; Our previous study find that high-dose multivitamin may decrease the expression of miR-758 and increase the level of Ang-2, suggesting that the high risk of breast cancer maybe associated with multivitamin induced angiogenesis by miR-758/Ang-2. Study apply positive and negative ways to verify the function of miR-758 in angiogenesis of breast cancer ; Meanwhile, taking Ang-2 as the point of the mechanism to reveal the action of miR-758. System evaluation of high dose of multivitamin increase the risk of breast cancer by miR -758/Ang –2. From the perspectives of relationship between nutrition and tumor, our study will reveal a novel function and mechanism of miR -758, providing new clues for the nutritional research of breast cancer.